Skip to main content
Egyptian Journal of Medical Human Genetics
Download PDF

Role of interleukins 12B and 17A genetic variation in house dust mites allergy

Egyptian Journal of Medical Human Genetics volume 21, Article number: 60 (2020) Cite this article

Abstract

Background

The house dust mites (HDM) constitute a major cause of allergic diseases all over the world. Genes encoding interleukins 12B and 17A which determine the course of T cell-mediated immune response are prime candidates as allergic disease susceptibility. The purpose of this study was to evaluate whether a single-nucleotide polymorphisms (SNP) of interleukins 12B + 1188A/C (rs3212227) and 17A −197G/A (rs2275913) confers susceptibility to HDM allergic diseases. Through a case-control study, 120 subjects served as 60 dust mites' allergic patients and 60 healthy non-allergic controls. Total immunoglobulin (Ig) E level, eosinophilic count, serum interleukins 4, 10, 12B, and 17A levels for the studied subjects were measured. Then, genotyping of single-nucleotide polymorphisms (SNPs) at +1188A/C for IL12B and −197G/A for IL17A gene were conducted using restriction fragment length polymorphisms (RFLP-PCR).

Results

The present study showed that in HDMs' allergic subjects there was a significant increase in IL12B (+1188 A/C) and IL17A (−197 G/A) genotype variants compared to that of the controls. There was a significant increase in total IgE levels, eosinophil counts, and the levels of both IL-4 and IL-17A, while IL12B was significantly lower in patients compared to that of the controls. There was no significant difference in IL-10 levels between patients and controls.                                                                            

Conclusion

Our findings indicate that IL12B (+1188 A/C) and IL17A (−197G/A) might be associated with an increase in the susceptibility to dust mites’ allergic patients.

Background

Allergic diseases are now one of the top conditions in the twenty-first century requiring a lot of effort for prevention and control. Allergic diseases are still largely unclear despite abundant research. Up to 25% of the world’s population is suffering from allergic conditions such as asthma, allergic rhinitis, and allergic dermatitis [1]. Allergy is an IgE-mediated disease caused by allergens sensitization. These previously mentioned allergic diseases are the most common familial IgE-related diseases [2]. The house dust mites (HDM) are the main cause of allergic stimulation in patients with atopic conditions [3, 4].

Allergy is caused by an interaction between environmental and genetic factors [5]. Atopy development depends on multiple genes that affect the expression of disease. Various genome-wide searches have related atopy development to specific autosomal chromosomal regions [6]. Among populations, genes that predispose individuals to allergy are not consistent. In this regard, Th1 and Th2 cytokines and their gene polymorphism seem significant. These cytokines genes polymorphisms could affect the transcription of the genes, causing inter-individual variations in the production of cytokines [7].

The existence of a single-nucleotide polymorphism (SNP) at 3′UTR +1188 A/C is linked to the production of IL-12B in various pathologies affecting the Th1/Th2 balance [8], susceptibility and severity of different types diseases [9, 10]. Polymorphism of the gene IL-17A (rs2275913 G/A) has a significant role in the activity of interleukin by modifying the role of cytokine and regulation of its expression [11]. However, the association between such polymorphisms and the immune response in an allergy to dust mites was not explored. We studied the polymorphic region in IL-12 p40 (3′UTR +1188 A/C) and IL17A (−197G/A) and the potential correlation of dust mites' allergy susceptibility in Egyptian patients.

The initial exposure to HDM allergens in predisposed individuals contributes to the activation of the allergen-specific T-helper 2 (Th2) cells and the synthesis of IgE. Allergy has been associated with several cytokines involved in the inflammation and immunoregulation pathways [12].

Interleukin (IL)-4 is a pro-inflammatory interleukin that has long been associated with allergic disorder pathogenesis. This cytokine plays a role in the onset and propagation of allergic inflammation [13]. IL-10 is a pleiotropic anti-inflammatory interleukin that functions mainly by suppressing the pro-inflammatory cytokines [14].

IL-12 is a heterodimer cytokine formed by a 35 kDa chain (p35 or IL-12A) and a 40 kDa chain (p40 or IL-12B). IL-12B is encoded by the IL12B gene located on 5q31–33 and because of its pro-inflammatory and immunoregulatory activities it might be an important functional candidate gene for inflammatory diseases. IL12B induces the production of interferon-γ (IFN-γ), favors the differentiation of T helper 1 (Th1) cells, and it is a connecting point for innate and adaptive immunity [15].

The IL-17 cytokine family includes six members (A–F). IL-17A is a proinflammatory cytokine that upregulates several cytokines and chemokines, leading to the recruitment of neutrophils to sites of inflammation [16]. Several studies have shown a strong association between IL-17A and neutrophil inflammation, involving IL-17A as a possible candidate gene to predict allergy susceptibility [17, 18].

Methods

Ethics approval and consent to participate

The study had the required approval from the ethical committee of the Faculty of Medicine Ain Shams University. Written informed consent has been obtained from all participants. Patients found allergic to dust mites have been referred for immunotherapy whenever accepted by them.

Study population

The population of this study included a total of 120 subjects; dust mites' allergic patients (n = 60) and controls (n = 60). We enrolled dust mites’ allergic patients, from the Allergy and Clinical Immunology outpatient clinic in the tertiary teaching hospital (Ain Shams University Hospitals, Egypt). The criteria for study inclusion were adults patients over 18 years of age, those who were diagnosed with dust mites allergic diseases (asthma, allergic rhinitis, and allergic dermatitis) by an allergy specialist by history, physical examination, and positive skin prick test results using prepared mixed dust mites crude extracts. Asthma was diagnosed based on GINA guidelines, 2018 [19] with typical symptoms and signs, including wheezing, shortness of breath, chest tightness, or cough. Allergic rhinitis was based on ARIA guidelines, 2010 [20] with symptoms and signs of rhinorrhea, nasal obstruction, and itching sensation or sneezing. We assessed if the symptoms of allergic diseases were aggravated after exposure to mites (e.g., after bedding, cleaning a closet, or sleeping on an old bed). Atopic dermatitis was diagnosed when atopy was associated with chronic relapsing eczematous dermatitis with pruritis [21].

Controls criteria included: adults over 18 years of age with no symptoms or history of allergic diseases, negative skin prick test results for prepared mixed dust mites crude extract. Patients on specific allergen immunotherapy, pregnant women, patients on corticosteroids, oral antihistamines, or any other drugs that inhibit skin prick test reactions, and patients with positive dermographism were excluded from the study.

Preparation of dust mites crude extract

Mixed crude mite extraction was carried out as follows: the mite extract was prepared from mixed species of dust mites by extracting pure mites at a final concentration of 1:10 w/v in Coca solution (2.5 gm sodium bicarbonate (NaHCO3), 5 gm sodium chloride (NaCl), 5 gm phenol crystals and 1000 ml sterile water for injection) under a laminar flow cabinet with sterile technique. The mixture of mites and Coca solution was magnetically stirred at room temperature for 1 h. The solution was filtrated twice, first through Whatman No. 1 filter paper (11μm), and then pass through a 0.2-micron filter using the Vacuum filtering apparatus. The mite extract was stored at 4 °C and was used within 3 months. Mixed crude mites extraction was carried out at the Allergy laboratory at the Allergy Medicine Unit, Internal Medicine Department, Ain-Shams University hospital, Egypt [22].

Skin prick test

Skin prick tests were carried out using prepared mixed dust mites crude extracts, as recommended by the European Academy of Allergy and Clinical Immunology. Saline was used as control negative and histamine as control positive. Skin testing was considered positive if a mixed crude extract of prepared dust mites elicits a wheal reaction of > 3 mm in diameter after 15 min. Before clinical evaluation, none of the participants received antihistamines, systemic, or topical corticosteroids 3 weeks before [23].

Blood samples collection

A 6-ml blood sample was taken and divided into 2 portions: whole blood for DNA extraction and eosinophil Counts. Serum samples for total levels of IgE and interleukins measures [24].

Eosinophil count and total serum immunoglobulin E determinations

A complete blood picture was performed to determine the eosinophilic count in the peripheral blood. Total IgE level was measured by ELISA using the Manufacturer's protocol based on the BIOS IgE Quantitative Kits (South San Francisco, USA). The Assay sensitivity was 5.0 IU/ml for total IgE.

Detection of serum interleukins

The serum levels of IL-4, IL-10, IL12B, and IL-17A were measured simultaneously with the Magnetic Luminex Multianalyte technology. The test was conducted as instructed by the manufacturer (R&D Systems, Bio-Techn Assay Kit, USA). Data were analyzed using the Luminex Labscan 100 Multiplexing System (USA, Model No: LX10007073403). The reading for the concentration of each cytokine was detected by the instrument as the mean fluorescence intensity (MFI). These results were subsequently converted from a set of standards that were running concurrently in the assay to pg/ml of cytokine-dependent on the MFI values.

DNA extraction

Genomic DNA was extracted from 200 μl of whole blood using the QIAamp ® DNA Blood Mini Kit (Qiagen, Germany) according to the Blood and Body Fluid Spin Protocol in the accompanying manual. After the DNA was extracted, the samples were labeled and stored at − 20 °C.

IL12B and IL17A polymorphisms

The genotypes of IL-12B rs3212227 and IL-17A rs2275913 were analyzed using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method according to Youssef [25] for IL12B and Hammad [26] for IL17A. Genomic DNA from the cases and controls were subjected to PCR analysis of the IL-12B and IL17A genes. The sequence of primers (Invitrogen; Thermo Fisher Scientific, Inc., Waltham, MA, USA) used are presented in Table 1

Table 1 IL-12B and IL-17A primers sequence
Full size table

The reaction volume was 25 ul: 5 ul extracted DNA, 12.5 ul Hot Star-Taq® PCR master mix (Qiagen, Germany), 0.5 ul of each primer, and 6.5 ul RNase-free water.

Reaction conditions were carried out in Thermo Scientific HBPXE02110 PXE 0.2 Thermal Cycler (USA) with the following cycling parameters for IL-12B, an initial 95 °C for 15 min followed by 40 cycles of 94 °C for 45 s, 43 °C for 1 min, and 72 °C for 45 s and a final extension at 72 °C for 5 min. For IL-17A, the PCR conditions included an initial 95 °C for 15 min followed by 40 cycles of 94 °C for 45 s, 58.5 °C for 1 min, and 72 °C for 45 s and a final extension at 72 °C for 10 min. Ten microliters of PCR products were evaluated in 2% agarose gel to check the PCR products at 233 base pairs (bp) for IL12B and 344 bp for IL17A Figs. 1 and 2.

Fig. 1
figure1

Results of agarose electrophoresis of the interleukin (IL)-12B rs3212227 polymorphism. a Represent the PCR amplified product at 233 bp. b Represent the restriction fragment length polymorphism analysis reaction (RFLP). Lanes 3, 4, 5, and 6 represent the interleukin (IL)-12 AC genotype (three bands at 233, 165, and 68 bp). Lanes 7 and 8 represent the IL-12 CC genotype (two bands at 165 and 68 bp). Lanes 1 and 2 represent the IL-12 AA genotype (one band at 233 bp). The ladder is a 50-bp molecular-weight marker

Full size image
Fig. 2
figure2

Results of agarose electrophoresis of the interleukin IL-17 A rs2275913. a Represent the PCR amplified product at 344bp. b Represent the restriction fragment length polymorphism analysis reaction (RFLP). Lanes 1, 3, 5, and 7 represent the GA genotype (three bands at 344, 213, and 131 bp). Lanes 6 and 9 represents the AA genotype (two bands at 213 and 131 bp). Lanes 2, 4, and 8 represent the GG genotype (single band at 344 bp). The ladder is a 50-bp molecular-weight marker

Full size image

RFLP analysis for IL12B was done using Taq-1 restriction enzyme (Promega, Southampton, UK). For IL17A, RFLP analysis was done using XmnI restriction enzyme (Thermo Fisher Scientific, Waltham, MA, USA). DNA fragments were resolved in 2.5% agarose gels. The results of genotyping were confirmed by randomly assaying 10% of the original specimens for replicate to exclude genotyping errors. There were no differences between genotypes identified in duplicate.

Statistical analysis

Analysis of the data was done using SPSS software (Statistical Package for the Social Sciences) version 20. Statistical presentation and analysis of the present study were conducted, using the mean, standard deviation, Student’s t test, Fisher exact test, and Analysis of variance [ANOVA] tests.

Results

This is a case-control study that was conducted on patients selected from the outpatient clinic of Allergy and Clinical Immunology at the tertiary hospital. It included 60 patients with dust mites' allergy and 60 non-allergic persons as control. The range of age was between 19 and 50 years old. They were 72 (60%) females and 48 (40%) males. The enrolled studied groups were divided into 2 groups according to the results of skin prick tests which was considered positive if prepared dust mites crude extract elicit a wheal reaction > 3 mm in diameter after 15 min. into cases (dust mites allergic patients with positive skin prick tests) and controls (non-allergic persons with negative skin prick tests). The enrolled patients were divided into three groups according to clinical presentation into asthmatic, Allergic Rhinitis (AR), and dermatitis patients.

Comparison of demographic features between the studied groups

Comparison of demographic features between the studied groups revealed that there was a statistically non-significant difference between the studied groups regarding age, gender, residence, occupation, smoking, and deal with animals (Tables 2 and 3).

Table 2 Comparison between dust mites' allergic patients and controls regarding demographic characteristics
Full size table
Table 3 Comparison of the studied groups regarding demographic characteristics
Full size table

Student’s t test was used. Age is represented as mean and SD, while gender, residence, occupation, smoking, and deal with animals are represented as number and percent

Eosinophil count and total IgE levels

Peripheral blood eosinophil cell counts (PBEC) were found to be significantly higher at p < 0.001 in mites’ allergic patients (mean value was 576.9 ± 60.03 cells/mm3) compared to the controls group (mean value was 142.9 ± 31.0 cells/mm3). Our results revealed a significant elevation in PBEC in asthma, allergic rhinitis, and dermatitis compared with controls (mean values for PBEC were 636.3 cells/mm3, 576.9 cells/mm3, and 517.7 cells/mm3, respectively; p < .001 for each group)

Total serum IgE levels were found to be significantly higher at p < 0.001 in mites allergic patients (mean values was 276.9 ± 141.2 IU/ml) compared to the controls group (mean values was 15.5 ± 15.9 IU/ml).

Our results showed a significant elevation in total serum IgE levels in asthma, allergic rhinitis, and dermatitis compared with controls (mean values for total serum IgE levels were 342.0 IU/ml, 226.9 IU/ml, and 262.0 IU/ml respectively; p < .001 for each group) as shown in Figs. 3 and 4, Tables 4 and 5.

Fig. 3
figure3

a A graph comparing the total PBEC in patients and controls. b A graph comparing the total IgE levels in patients and controls. c A graph comparing IL4, 10, 12B, and 17A levels in patients and controls. All parameters represented as mean.

Full size image
Fig. 4
figure4

a A graph comparing the total PBEC in patients’ subgroups and controls. b A graph comparing the total IgE levels in patients’ subgroups and controls. c A graph comparing IL4, 10, 12B, and 17A levels in patients’ subgroups and controls. All parameters represented as mean.

Full size image
Table 4 Comparison between dust mites' allergic patients and controls regarding laboratory data (IgE levels, eosinophilic count, and interleukins levels)
Full size table
Table 5 Comparison between the studied subgroups regarding laboratory data (IgE levels, eosinophilic count, and interleukins levels)
Full size table

Serum levels of the studied cytokines

IL-4, 10, 12B, and 17A serum cytokines levels were assessed in dust mites' allergic patients and controls group. The level of IL-4 had a significant difference between dust mites' allergic patients compared with the controls group (p < 0.001). The mean value of allergic patients was (44.76 ± 6.3 pg/ml) while in the controls group was (6.72 ± 0.47 pg/ml). Our results showed a significant elevation in IL 4 levels in asthma, allergic rhinitis, and dermatitis compared with controls (mean values were 51.3 pg/ml, 41.5 pg/ml, and 41.5 pg/ml respectively; p < .001 for each group).

The level of IL-17A had a significant difference between dust mites' allergic patients compared with the controls group (p < 0.001). The mean value of allergic patients was 32.2 ± 9.2 pg/ml while in the control group was 3.31 ± 0.85 pg/ml. The results revealed a significant elevation in IL 17A levels in asthma, allergic rhinitis, and dermatitis compared with controls (mean values were 42.2 pg/ml, 32.2 pg/ml, and 22.2 pg/ml, respectively; p < .001 for each group) (Figs. 3 and 4).

On the other hand, the IL 12B level was significantly (p < 0.001) lower in patients than controls. The mean value of patients was 170.49 ± 50.72 pg/ml while in the control group was 264.46 ± 31.35 pg/ml. The mean values of IL12B levels were significantly lower in asthma, allergic rhinitis, and dermatitis compared with controls (144.1 pg/ml, 144.1 pg/ml, and 223.3 pg/ml respectively).

Regarding IL 10 level, there was a statistically non-significant difference (p > 0.05) between the studied groups. The mean value of patients was 2.8 ± 1.2 pg/ml while in the control group was 3.5 ± 0.45 pg/ml. Level of IL-10 had no significant difference in asthma, allergic rhinitis, and dermatitis compared with controls (mean values were 2.9 pg/ml, 2.9 pg/ml, and 2.6 pg/ml, respectively; p < .001 for each group) as demonstrated in Tables 4 and 5.

Genotype and allele frequencies of IL12B (1188 A/C)

As regards the results of PCR-RFLP for IL12B (+1188 A/C) gene polymorphism in the studied groups (whole 120 persons), the PCR product was at 344 bp. Genotyping results by the PCR–RFLP showed the existence of the 3 genotypes of the IL-12B rs3212227 polymorphism (AA, AC, and CC), and examples of these results are shown in Fig. 1. Genotypes were determined as follows, AA (233 bp), AC (233, 165, 68 bp), and CC (165, 68 bp). The homozygous genotype (C/C) was detected in 2/120 persons (1.66%) (2/60 patients (3.3%) and 0/60 persons (0%) in the control group). The heterozygous genotype (A\C) was detected in 46/120 persons (38.3%) (40/60 patients (66.7%) and 6/60 persons (10 %) in the control group). The homozygous genotype (A\A) was detected in 72/120 patients (60%) (18/60 patients (30%) and 54/60 persons (90%) in the control group).

There was a statistically significant difference between the studied groups regarding IL 12B polymorphism and alleles as demonstrated in Table 6, Figs 5 and 6. Table 7 Genotype and allele frequencies of IL12B (+1188 A/C) and IL17A (−197G/A) polymorphisms among studied groupsIL 12B AA genotype was highly significantly lower (p value ≤ 0.01) in patients than controls (Table 7, Figs. 5 and 6). On the other hand, AC and CC genotypes showed a highly significant difference in patients compared with the controls group (p value ≤ 0.01). Distribution of alleles frequency of IL12B (+1188 A/C) in all studied groups (120 persons) was as the following: the frequency of A allele was 79.2%, while the frequency of C allele was 20.8%. An allele was significantly higher in controls compared with patients. On the other hand, the C allele was significantly higher in patients compared with the control group (p value ≤ 0.01).

Table 6 Genotype and allele frequencies of IL12B (1188 A/C) and IL17A (−197G/A) polymorphisms in patients and controls
Full size table
Fig. 5
figure5

a, b Genotypes and alleles frequencies of IL12B (1188 A/C) in patients and controls. c, d Genotypes and alleles frequencies of IL17A (−197G/A) in patients and controls. Polymorphisms are represented as a percent

Full size image
Fig. 6
figure6

a, b Genotypes and alleles frequencies of IL12B (+1188 A/C) in patients’ subgroups and controls. c, d Genotypes and alleles frequencies of IL17A (−197G/A) in patients’ subgroups and controls. Polymorphisms are represented as a percent.

Full size image
Table 7 Genotype and allele frequencies of IL12B (+1188 A/C) and IL17A (−197G/A) polymorphisms among studied groups
Full size table

Genotype and allele frequencies of IL17A (−197G/A) polymorphism

As regards the results of PCR-RFLP for IL17A (−197G/A) gene polymorphism in the studied groups (whole 120 persons), the PCR product was at 344 bp. Genotyping results by the PCR–RFLP showed the existence of the 3 genotypes of the IL-17A rs2275913 polymorphism (GG, GA, and AA), and examples of these results are shown in Fig. 2. Genotypes were determined as follows: GG (344 bp), GA (344, 213, 131 bp), and AA (213, 131 bp).

The homozygous genotype (A/A) was detected in 12/120 persons (10%) (6/60 patients (10%) and 6/60 persons (10%) in the control group). The heterozygous genotype (G\A) was detected in 44/120 persons (36.6%) (38/60 patients (63.3%) and 6/60 persons (10 %) in the control group). The homozygous genotype (G\G) was detected in 64/120 persons (53.3%) (16/60 patients (26.7%) and 48/60 persons (80%) in the control group).

There  was a statistically significant difference between AR and dermatitis allergic patients compared with the control group (p < 0.05) as showed in Tables 6 and 7.

IL 17A GG genotype was significantly fewer in patients than controls. On the other hand, GA genotypes were significantly higher in patients compared with the control group (p < 0.05). There was a statistically non-significant difference in genotyping (p > 0.05) between the asthmatic group and controls. Distribution of alleles frequency of IL17A (−197G/A) in all studied population (120 persons): the frequency of the G allele was 71.7%, while the frequency of A alleles was 28.3%. G allele  was significantly higher in controls compared with patients. On the other hand, A allele was significantly higher in patients compared with the control group (p value ≤ 0.01).

Genotypes of IL12B (+1188 A/C) polymorphism and its effect on IgE and IL-12B serum levels

There was a statistically non-significant difference between gene polymorphism and IgE and IL-12B serum levels as shown in Table 8.

Table 8 Effect of IL-12B gene polymorphism in allergic patients on IgE and IL-12B serum levels in dust mites' allergic patient
Full size table

Genotypes of IL17A (−197G/A) polymorphism and its effect on IgE and IL17A serum levels

There was a statistically non-significant difference between IL-17A gene polymorphism and IgE and IL-17A serum levels as demonstrated in Table 9.

Table 9 Effect of IL-17A gene polymorphism on IgE and IL-17A serum levels in domestic mites' allergic patient
Full size table

Discussion

Allergy is an inflammatory and immune disorder caused by aberrant T helper-2 (Th2) immune reactions caused by excessive exogenous stimulation triggering the IgE receptor to secrete pro-inflammatory cytokines [18]. The differentiation of CD4+ T cells into effectors generating Th2 cytokine profiles, such as IL-4, IL-5, IL-9, and IL-13, is the initial event and the major factor in the development of atopic diseases [27, 28].

In the present study, we found that the peripheral blood eosinophil count was significantly higher in patients with atopy than in the control group. Studies on atopic patients in different areas have shown similar results [6, 29].

We also observed that total IgE was higher in atopic patients than in controls. Similar results have been reported in many studies with allergic patients [6, 30,31,32,33].

According to measured interleukins levels in our study, the serum level of IL-4 in dust mites allergic patients was significantly higher relative to the control group. IL-4 has been identified as the most important cytokine implicated in the upregulation of in vivo IgE production related to the intensity of eosinophilic inflammation in allergic populations [34]. Elevation of serum IL-4 in allergy was observed in allergic patients and indicated involvement in the allergy pathogenesis [27]. Similar findings have been obtained in other studies in asthma and other atopic diseases [35, 36].

In this study, there was no significant difference in IL-10 serum levels between patients and controls as was previously shown in a study with atopic asthma children from Saudi Arabia [24]. Etiology of allergic inflammation in tissues has been related to increased IL-4 and decreased IL-10 levels in the blood [37]. On the other hand, the increased expression of IL-10 was documented in allergy [38, 39]. Such conflicting results can be explained by the fact that the role of IL10 relates not only to its level but also to other factors including its binding affinity to its receptors. IL-10 may have a positive or negative effect on IgE either by triggering IgE release from plasma cells or by suppressing IgE isotype switches by inhibiting IL-4 and IL-13 [40]. Therefore, IL-10 can have various results, depending on the timing and source. If present early in the immune response, IL-10 should induce allergen non-responsiveness and prevent IgE isotype switching, whereas if present late in the allergic response, IgE secretion by B lymphocytes may be enhanced [41].

IL-12 has multiple biological activities, and it is a key factor that drives Th1 responses and IFN-γ production [42]. Our results demonstrated a significantly lower serum level of IL12B in patients with dust mites allergy as compared to controls as shown in several studies where IL-12 mRNA expression and IL12b levels were lower in atopic patients compared to controls [43,44,45].

In this study, increased IL-17A levels were detected higher in the serum of dust mites allergic patients as compared to controls. As shown in studies with allergic patients [46, 47]. IL17A works on epithelial cells and other types of inflammatory cells to enhance the secretion of pro-inflammatory cytokines and stimulate neutrophil recruitment [46]. Upregulation of IL-17A in plasma allergic patients can be partly related to increased production of circulating Th17 cells, which are the primary source of IL-17 in vivo [48]. Several studies have shown that IL-17A has been locally increased in bronchial biopsies, bronchoalveolar lavage fluid, and sputum samples from asthmatic patients compared to controls [49, 50] and raised in IL17A in plasma of allergic asthmatics than in controls [51].

Recent studies have suggested that certain molecules’ SNPs affect their level of expression or function [52]. Numerous molecules, including cytokines, are now believed to be associated with the pathogenesis of immune-mediated diseases, and some of these molecules’ gene polymorphisms are considered candidates as genetic factors in these diseases. In this study, we aimed to investigate the possible association between the interleukin 12B polymorphism rs3212227 and IL17A polymorphism rs2275913 with dust mites’ allergic patients.

Our results showed that the frequencies of IL12B A/C and C/C genotypes were significantly higher in patients compared with the control group (p value ≤ 0.01). AA genotype tended to be decreased in allergic patients compared with controls, and the reverse was true in CC genotype. We demonstrated that the A allele was decreased in allergic patients, compared with control with a significant difference. These results indicate that the IL-12 p40 3′UTR +1188 A/C polymorphism is associated with susceptibility to dust mites allergy in Egyptian patients as presented in a study where the A allele was decreased in atopic dermatitis [8] and other studies showed an increase in C alleles among asthmatic patients [53] and allergic rhinitis [54].

The CC genotype carriers were significantly overrepresented among autoimmune diseases as in ulcerative colitis, Crohn’s disease [52], and lepromatous leprosy patients [55].

Our results demonstrated that dust mites' allergic patients presented with higher frequencies of GA genotype in rs2275913 of IL-17A than healthy controls. These results are the same as several studies in asthmatic patients [53,54,55,56]. Also, previous researches demonstrated the role of IL17A (rs2275913) gene polymorphism in inflammatory and autoimmune diseases as rheumatoid arthritis [17] and ulcerative colitis [57].

In this study, there was no association between genotypes of the studied SNPs of IL12B and IL17A with their serum levels, as was reported by many studies that found no evidence of polymorphism effect on cytokine expression [55, 58]. However, our findings need to be interpreted with caution as it needs further prospective studies with larger sample sizes and diverse populations to confirm the relationship between IL12B and IL17A SNPs and allergy development.

Conclusion

To our knowledge, this research has for the first time identified a series of Th1/Th2 cytokine and +1188A/C IL12B and −197G/A IL17A SNPs associated with allergy to dust mites in Egyptian patients. IL-12B gene polymorphism at +1188 A/C and IL17A at  -197 G/A may be contributing factors in the susceptibility of dust mites’ allergy among patients. We found higher frequencies of IL12B rs3212227 AC and CC genotypes in patients compared with the control group (p value ≤ 0.01) and higher frequencies of GA genotype in rs2275913 of IL-17A than controls. These findings highlight the potential genetic influence on allergy development, and it may be possible to predict a particular individual’s susceptibility to HDM allergy and the development of new therapeutic strategies.

Availability of data and materials

The authors confirm that data supporting the findings of this study are available within the study.

Abbreviations

HDM:

House dust mites

IL:

Interleukin

PCR-RFLP:

Polymerase chain reaction-restriction fragment length polymorphisms

SNP:

Single-nucleotide polymorphisms

References

  1. 1.

    Al Dhduh MA, Sabri NA, Fouda EM (2015) Prevalence and severity of allergic diseases among Egyptian pediatric in different Egyptian areas. Int J Pharmaceutical Sci Res 14:2015. https://doi.org/10.15344/2394-1502/2015/107

    Article  Google Scholar 

  2. 2.

    Doll RJ, Joseph NI, McGarry D, Jhaveri D, Sher T, Hostoffer R (2019) Epidemiology of Allergic Diseases. In: Mahmoudi M (ed) Allergy and Asthma. Springer, Cham. https://doi.org/10.1007/978-3-030-05147-1

    Chapter  Google Scholar 

  3. 3.

    Salo PM, Arbes SJ Jr, Crockett PW, Thorne PS, Cohn RD, Zeldin DC (2008) Exposure to multiple indoor allergens in US homes and its relationship to asthma. J Allergy Clinical Immunology. 121(3):678–684. https://doi.org/10.1016/j.jaci.2007.12.1164

    CAS  Article  Google Scholar 

  4. 4.

    Pawankar R, Canonica GW, Holgate ST, Lockey RF, Blaiss M (2011) World Allergy Organization (WAO) white book on allergy. World Allergy Organisation, Wisconsin. https://doi.org/10.3388/jspaci.25.341

    Book  Google Scholar 

  5. 5.

    Jenerowicz D, Silny W, Danczak-Pazdrowska A, Polanska A, Osmola-Mankowska A, Olek-Hrab K (2012) Environmental factors and allergic diseases. Ann Agric Environmental Med 19:3

    Google Scholar 

  6. 6.

    Hussein YM, Ahmad AS, Ibrahem MM, El Tarhouny SA, Shalaby SM, Alshal AS, El Said M (2009) 6 Interferon Gamma Gene Polymorphism as a Biochemical Marker in Egyptian Atopic Patients. J Invest Allergology Clin Immunology 19(4):292

    CAS  Google Scholar 

  7. 7.

    Reynard MP, Turner D, Navarrete CV (2000) Allele frequencies of polymorphisms of the tumour necrosis factor-α, interleukin-10, interferon-γ and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenetics. 27(4):241–249. https://doi.org/10.1046/j.1365-2370.2000.00227.x

    CAS  Article  Google Scholar 

  8. 8.

    Tsunemi Y, Saeki H, Nakamura K, Sekiya T, Hirai K, Fujita H, Asano N, Kishimoto M, Tanida Y, Kakinuma T, Mitsui H (2002) Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J Dermatological Sci 30(2):161–166

    CAS  Article  Google Scholar 

  9. 9.

    Chen X, Han S, Wang S, Zhou X, Zhang M, Dong J, Shi X, Qian N, Wang X, Wei Q, Shen H (2009) Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clinical Cancer Res. 15(1):400–405. https://doi.org/10.1158/1078-0432.CCR-08-1829

    CAS  Article  Google Scholar 

  10. 10.

    Wei YS, Lan Y, Luo B, Lu D, Nong HB (2009) Association of variants in the interleukin-27 and interleukin-12 gene with nasopharyngeal carcinoma. Molecular Carcinogenesis: Published in cooperation with the University of Texas MD Anderson Cancer Center. 48(8):751–757. https://doi.org/10.1002/mc.20522

    CAS  Article  Google Scholar 

  11. 11.

    Moundir C, Chehab F, Senhaji N, Boufettal R, Idouz K, Erguibi D, Nadifi S (2019) Association of the IL-17A rs2275913 and MIF rs755622 polymorphisms with the risk of gastric and colorectal cancer. Meta Gene 22. https://doi.org/10.1016/j.mgene.2019.100605

  12. 12.

    Bossé Y, Hudson TJ (2007) Toward a comprehensive set of asthma susceptibility genes. Annu. Rev. Med. 58:171–184. https://doi.org/10.1146/annurev.med.58.071105.111738

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Gour N, Wills-Karp M (2015) IL-4 and IL-13 signaling in allergic airway disease. Cytokine. 75(1):68–78. https://doi.org/10.1016/j.cyto.2015.05.014

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Ciprandi G, Fenoglio D, Cirillo I, Vizzaccaro A, Ferrera A, Tosca MA, Puppo F (2005) Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report. Annals of Allergy, Asthma & Immunology. 95(1):38–44

    CAS  Article  Google Scholar 

  15. 15.

    Sanchez E, Morales S, Paco L, Lopez-Nevot MA, Hidalgo C, Jimenez-Alonso J, Torres B, Gonzalez-Gay MA, Callejas JL, Ortego-Centeno N, Sanchez-Roman J (2005) Interleukin 12 (IL12B), interleukin 12 receptor (IL12RB1) and interleukin 23 (IL23A) gene polymorphism in systemic lupus erythematosus. Rheumatology. 44(9):1136–1139. https://doi.org/10.1093/rheumatology/keh697

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Kaabachi W (2014) ben Amor A, Kaabachi S, Rafrafi A, Tizaoui K, Hamzaoui K. Interleukin-17A and-17F genes polymorphisms in lung cancer. Cytokine. 66(1):23–29. https://doi.org/10.1016/j.cyto.2013.12.012

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Kohyama K, Abe S, Kodaira K, Yukawa T, Hozawa S, Sagara H, Kurosawa M (2011) IL-13 and IL-17A gene polymorphisms in Japanese patients with aspirin-exacerbated respiratory disease. Annals of Allergy, Asthma & Immunology. 107(6):510–516

    CAS  Article  Google Scholar 

  18. 18.

    Wang Z, Potter CS, Sundberg JP, Hogenesch H (2012) SHARPIN is a key regulator of immune and inflammatory responses. Journal of cellular and molecular medicine. 16(10):2271–2279. https://doi.org/10.1111/j.1582-4934.2012.01574.x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Global strategy for asthma management and prevention (updated 2018): Global Initiative for Asthma (GINA). http://www.ginasthma.org. [Accessed 8 Oct 2018].

  20. 20.

    Brozek JL, Bousquet J, Baena-Cagnani CE et al (2010) Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 126:466–476

    Article  PubMed  Google Scholar 

  21. 21.

    Saeki H, Nakahara T, Tanaka A et al (2016) Clinical Practice Guidelines for the Management of Atopic Dermatitis 2016. J Dermatol 43:1117–1145

    Article  PubMed  Google Scholar 

  22. 22.

    Pacharn P, Kumjim S, Tattiyapong P, Jirapongsananuruk O, Piboonpocanun S (2016) Identification of wheat sensitization using an in-house wheat extract in Coca-10% alcohol solution in children with wheat anaphylaxis. Asian Pac J Allergy Immunology 1, 34(2) http://apjai-journal.org/wp-content/uploads/2016/10/30239-40016-4-PB-1.pdf

  23. 23.

    Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC (2012) Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 67(1):18–24. https://doi.org/10.1111/j.1398-9995.2011.02728.x

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Hussein YM, Alzahrani SS, Alharthi AA, Ghonaim MM, Alhazmi AS, Eed EM, Shalaby SM (2014) Association of serum cytokines levels, interleukin 10− 1082G/A and interferon-γ+ 874T/A polymorphisms with atopic asthma children from Saudi Arabia. Cellular Immunol 289(1-2):21–26. https://doi.org/10.1016/j.cellimm.2014.03.006

    CAS  Article  Google Scholar 

  25. 25.

    Youssef SS, Mostafa Abd El-Aal A, Saad A, Omran MH, El Zanaty T, Mohamed Seif S. Impact of IL12B gene rs 3212227 polymorphism on fibrosis, liver inflammation, and response to treatment in genotype 4 Egyptian hepatitis C patients. Disease markers. 2013;35(5):431-437; https://doi.org/10.1155/2013/627589.

  26. 26.

    Hammad A, Mosaad YM, Hammad EM, Elhanbly S, El-Bassiony SR, Al-Harrass MF, Eid R, Sharaf Eldein OA, Alsawah GA, Yahia S, Fawzy IM (2016 Jan 2) Interleukin-17A rs2275913, Interleukin-17F rs763780 and rs2397084 gene polymorphisms as possible risk factors in Juvenile lupus and lupus related nephritis. Autoimmunity. 49(1):31–40. https://doi.org/10.3109/08916934.2015.1101071

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Lee YC, Lee KH, Lee HB, Rhee YK (2001) Serum levels of interleukins (IL)-4, IL-5, IL-13, and interferon-γ in acute asthma. Journal of Asthma. 38(8):665–671. https://doi.org/10.1081/JAS-100107544

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Wills-Karp M (2004) Interleukin-13 in asthma pathogenesis. Immunological reviews. 202(1):175–190. https://doi.org/10.1111/j.0105-2896.2004.00215.x

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Wosinska-Becler K, Plewako H, Håkansson L, Rak S (2004 Jan) Cytokine production in peripheral blood cells during and outside the pollen season in birch-allergic patients and non-allergic controls. Clin Experimental Allergy 34(1):123–130. https://doi.org/10.1111/j.1365-2222.2004.01850.x

    CAS  Article  Google Scholar 

  30. 30.

    Kawai K, Kawai K, Kamei N, Kishimoto S (1992 May) Levels of Serum IgE, Serum Soluble-FcεRII, and FcεRII (+) Peripheral blood lymphocytes in atopic dermatitis. The Journal of dermatology. 19(5):285–292. https://doi.org/10.1111/j.1346-8138.1992.tb03226.x

    CAS  Article  Google Scholar 

  31. 31.

    Johansson SG, Lundahl J (2001) Asthma, atopy, and IgE: what is the link? Curr Allergy Asthma Rep 1(2):89–90. https://doi.org/10.1007/s11882-001-0071-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Staikūniene J, Sakalauskas R (2003) The immunological parameters and risk factors for pollen-induced allergic rhinitis and asthma. Medicina. 39(3):244–253

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Hussein YM, Abd Allah SH, Mahmoud S, Ahmed AS (2006) Impact of IL-13 gene mutations in atopic diseases. EJBMB. 24:123–127

    Google Scholar 

  34. 34.

    Bettiol J, Bartsch P, Louis R, De Groote D, Gevaerts Y, Louis E, Malaise M (2000) Cytokine production from peripheral whole blood in atopic and nonatopic asthmatics: relationship with blood and sputum eosinophilia and serum IgE levels. Allergy. 55(12):1134–1141. https://doi.org/10.1034/j.1398-9995.2000.00711.x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Boniface S, Magnan A (2003) Pathophysiology of the IgE-dependent reaction in respiratory allergy. Revue de pneumologie clinique. 59(2 Pt 1):77–83

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Velázquez BL, Segura DL, Barbosa DE, Vázquez MI, Tapia JG, Altamirano SC, Feria AJ (2004) Determination of interleukins and IgG4 in patients with allergic rhinitis with and without immunotherapy. Revista alergia Mexico (Tecamachalco, Puebla, Mexico: 1993) 51(4):139–144

    Google Scholar 

  37. 37.

    Ospel'nikova TP, Konishcheva A, Mazurina SA, Lizogub NV, Osipova VV Evaluation of the interferon system and major cytokines in patients with bronchial asthma. Zhurnal mikrobiologii, epidemiologii, i immunobiologii 2012(1):35–41

  38. 38.

    Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA (2003 May) IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33(5):1205–1214. https://doi.org/10.1002/eji.200322919

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Lee JH, Yu HH, Wang LC, Yang YH, Lin YT, Chiang BL (2007) The levels of CD4+ CD25+ regulatory T cells in paediatric patients with allergic rhinitis and bronchial asthma. Clinical & Experimental Immunology. 148(1):53–63. https://doi.org/10.1111/j.1365-2249.2007.03329.x

    CAS  Article  Google Scholar 

  40. 40.

    Ohmori H, Kanda T, Takai T, Hikida M (1995) Induction of antigen-specific IgE response in murine lymphocytes by IL-10. Immunology letters. 47(1-2):127–132

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Steinke JW, Barekzi E, Hagman J, Borish L (2004) Functional analysis of− 571 IL-10 promoter polymorphism reveals a repressor element controlled by Sp1. J Immunology 173(5):3215–3222. https://doi.org/10.4049/jimmunol.173.5.3215

    CAS  Article  Google Scholar 

  42. 42.

    Silva DO, Correia NA, de Barros FT, de Lima LP, Morais A, Hassan R, Dellalibera E, de Mendonça Cavalcanti MD, Muniz MT (2019) 3′ untranslated region A> C (rs3212227) polymorphism of Interleukin 12B gene as a potential risk factor for Hodgkin’s lymphoma in Brazilian children and adolescents. Tumor Biology. 41(7):1010428319860400

    Article  PubMed  Google Scholar 

  43. 43.

    Naseer T, Minshall EM, Leung DY, Laberge S, Ernst P, Martin RJ, Hamid Q (1997) Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy. American journal of respiratory and critical care medicine. 155(3):845–851. https://doi.org/10.1164/ajrccm.155.3.9117015

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Nutku E, Gounni AS, Olivenstein R, Hamid Q (2000) Evidence for expression of eosinophil-associated IL-12 messenger RNA and immunoreactivity in bronchial asthma. Journal of allergy and clinical immunology. 106(2):288–292. https://doi.org/10.1067/mai.2000.107932

    CAS  Article  Google Scholar 

  45. 45.

    Xu Z, Pei L, Zhang F, Hu X, Gui Y, Wang L, Wu B (2013) A functional variant in IL12B promoter modulates its expression and associates with increased risk of allergic asthma. Genes & Immunity. 14(4):238–243. https://doi.org/10.1038/gene.2013.13

    CAS  Article  Google Scholar 

  46. 46.

    Schnyder-Candrian S, Togbe D, Couillin I, Mercier I, Brombacher F, Quesniaux V, Fossiez F, Ryffel B, Schnyder B (2006) Interleukin-17 is a negative regulator of established allergic asthma. J Exper Med 203(12):2715–2725. https://doi.org/10.1084/jem.20061401

    CAS  Article  Google Scholar 

  47. 47.

    Ciprandi G, De Amici M, Murdaca G, Fenoglio D, Ricciardolo F, Marseglia G, Tosca M (2009) Serum interleukin-17 levels are related to clinical severity in allergic rhinitis. Allergy. 64(9):1375–1378. https://doi.org/10.1111/j.1398-9995.2009.02010.x

    CAS  Article  Google Scholar 

  48. 48.

    Wakashin H, Hirose K, Maezawa Y, Kagami SI, Suto A, Watanabe N, Saito Y, Hatano M, Tokuhisa T, Iwakura Y, Puccetti P (2008 Nov 15) IL-23 and Th17 cells enhance Th2-cell–mediated eosinophilic airway inflammation in mice. Am J Respir Crit Care Med 178(10):1023–1032. https://doi.org/10.1164/rccm.200801-086OC

    CAS  Article  Google Scholar 

  49. 49.

    Molet S, Hamid Q, Davoineb F, Nutku E, Tahaa R, Pagé N, Olivenstein R, Elias J, Chakir J (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. Journal of Allergy and Clinical Immunology. 108(3):430–438. https://doi.org/10.1067/mai.2001.117929

    CAS  Article  Google Scholar 

  50. 50.

    Pène J, Chevalier S, Preisser L, Vénéreau E, Guilleux MH, Ghannam S, Molès JP, Danger Y, Ravon E, Lesaux S, Yssel H (2008 Jun 1) Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunology 180(11):7423–7430. https://doi.org/10.4049/jimmunol.180.11.7423

    Article  Google Scholar 

  51. 51.

    Zhao Y, Yang J, Gao YD, Guo W (2010) Th17 immunity in patients with allergic asthma. Int Arch Allergy Immunology 151(4):297–307. https://doi.org/10.1159/000250438

    CAS  Article  Google Scholar 

  52. 52.

    Daryani NE, Sadr M, Soltani S, Saghazadeh A, Moossavi S, Shahkarami S, Farhadi E, Rezaei N (2019) Association of T helper 1 cytokine gene single nucleotide polymorphisms with ulcerative colitis and Crohn’s disease. Digestive Dis 37(1):21–32. https://doi.org/10.1159/000492027

    Article  Google Scholar 

  53. 53.

    Padrón-Morales J, Sanz C, Dávila I, Munoz-Bellido F, Lorente F, Isidoro-Garcia M (2013) Polymorphisms of the IL12B, IL1B, and TNFA genes and susceptibility to asthma. J Investig Allergol Clin Immunol 23(7):487–494

    PubMed  Google Scholar 

  54. 54.

    Wei P, Kou W, Zhang C, Kang H, Yao H, Tang X, Wang W (2016) Genetic variations in interleukin-12B in allergic rhinitis. Immunologic research. 64(1):329–336. https://doi.org/10.1007/s12026-015-8758-6

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Alvarado-Navarro A, Montoya-Buelna M, Muñoz-Valle JF, López-Roa RI, Guillén-Vargas C, Fafutis-Morris M (2008) The 3′ UTR 1188 A/C polymorphism in the interleukin-12p40 gene (IL-12B) is associated with lepromatous leprosy in the west of Mexico. Immunology letters. 118(2):148–151

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Wang JY, Shyur SD, Wang WH, Liou YH, Lin CG, Wu YJ, Wu LS (2009) The polymorphisms of interleukin 17A (IL17A) gene and its association with pediatric asthma in Taiwanese population. Allergy. 64(7):1056–1060. https://doi.org/10.1111/j.1398-9995.2009.01950.x

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, Fujita H, Nakamura M, Yoshioka D, Arima Y, Okubo M (2008) The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. Journal of clinical immunology. 28(1):44–49. https://doi.org/10.1007/s10875-007-9125-8

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Arababadi MK, Pourfathollah AA, Jafarzadeh A, Hassanshahi G, Daneshmandi S, Shamsizadeh A, Kennedy D (2011) Non-association of IL-12+ 1188 and IFN-γ+ 874 polymorphisms with cytokines serum level in occult HBV infected patients. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association. 17(1):30. https://doi.org/10.4103/1319-3767.74461

    Article  Google Scholar 

Download references

Acknowledgements

The authors are very grateful to all the members of the Allergy Laboratory at the Allergy Medicine Unit, Department of Internal Medicine, Ain-Shams University Hospital.

Funding

The research work was self-funded.

Author information

Affiliations

  1. Medical Parasitology Department, Ain-Shams University, Ramsis Street, Abbassia Square, Cairo, Egypt

    Asmaa Mostafa Ammar, Elham Abbas EL. Zayyat, Amira EL. Saady Khayyal, Dina Mamdouh Hamdy & Noha Abdel Fattah Elleboudy

  2. Internal Medicine, Allergy and Clinical Immunology Department, Faculty of Medicine, Ain-Shams University, Ramsis Street, Abbassia Square, Cairo, Egypt

    Aya EL-Gendy

Authors
  1. Asmaa Mostafa Ammar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elham Abbas EL. Zayyat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amira EL. Saady Khayyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dina Mamdouh Hamdy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aya EL-Gendy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Noha Abdel Fattah Elleboudy
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NE and AA were involved in protocol development, researched the literature with EE, and conceived the study and laboratory work, then helped and revised the statistical work and results, and wrote the first draft of the manuscript. AA and AK conceived the study and were involved in the laboratory work and revised the statistical work and results. DH and AE helped in gaining ethical approval and patient recruitment. All of the authors help in data analysis. All authors reviewed, edited the manuscript, and approved the final version of this manuscript.

Corresponding author

Correspondence to Asmaa Mostafa Ammar.

Ethics declarations

Ethics approval and consent to participate

The study was been done according to the regulations of the Egyptian Ministry of Higher Education and after having the required approval from the ethical committee of the Faculty of Medicine Ain Shams University (No. FWA 000017585). Written informed consent was obtained from all participants. Patients found allergic to dust mites were referred for immunotherapy whenever accepted by patients.

Consent for publication

Not applicable.

Competing interests

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ammar, A.M., EL. Zayyat, E.A., Khayyal, A.E. et al. Role of interleukins 12B and 17A genetic variation in house dust mites allergy. Egypt J Med Hum Genet 21, 60 (2020). https://doi.org/10.1186/s43042-020-00098-w

Download citation