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Polymorphism of the IL-10 gene in Azeri population of Iran

Abstract

Background

Interleukin (IL)-10 is one of the key interleukins in the immune system. It plays an anti-inflammatory role in body by inhibition of the synthesis of pro-inflammatory cytokines and reducing the expression of major histocompatibility complex II molecules. The single-nucleotide polymorphism in the gene of this interleukin affects its expression level. Thus, this study was conducted to investigate the IL-10 gene polymorphism at position -1082A/G in Azeri population of Iran.

Methods

Blood samples were taken from 254 healthy and non-relevant Iranian Azeri individuals. After DNA extraction, the frequency of IL-10 genotypes and alleles at -1082A/G position was determined by allele specific-PCR method. Then, q-square test was used to compare allele frequencies and IL-10 genotypes with other populations, and p value of < 0.05 was considered significant.

Results

In Iranian Azeri population, the frequency percentage of AA, AG and GG genotypes in IL-10 gene at the -1082A/G location was 37.4, 43.3 and 19.3%, respectively. The frequency percentage of A and G alleles also were 59.1 and 40.9%, respectively. Based on statistical analysis, frequency of IL-10 genotypes in the current study was very similar to the population of Saudi Arabia, but it had a significant difference with East Asia and Ireland populations.

Conclusion

Results of the present study indicate similar polymorphism of IL-10 genotype with neighbor ethnicities in Middle East country. Based on patients backgrounds mentioned in their questioners, this polymorphism was associated with the susceptibility to asthma and Alzheimer in this population which are common in the region.

Background

Cytokines are hormone-like intercellular mediators that are produced during immunological responses. They regulate the immune system and modulate immune responses by regulating the growth, migration and differentiation of cells, especially leukocytes [1]. IL-10 is a class-II cytokine with the strongest anti-inflammatory activity, and it plays a central role in innate and adaptive immune system. IL-10 is mostly produced by T helper(Th)2 cells, but numerous other immune cells like regulatory T cells, Th1 cells, macrophages, natural killer cells(NK-cells), dendritic cells, mast cells, B cells, neutrophils and eosinophils also produce IL-10 [2, 3]. IL-10 influences a variety of cells and suppresses inflammatory responses through the blocking of pro-inflammatory cytokines production and reducing the expression of MHCII molecules. IL-10 also minimizes the host injury by acting on Th1 cells and macrophages and inhibits the secretion of pro-inflammatory cytokines including IFN-γ, IL-1 and IL-6 [4, 5]. The type and severity of stimulation, as well as the individual’s genetic makeup, influence IL-10 secretion. The human IL‐10 gene is located on the long arm of chromosome and spans about 4.7 kb, with 5 exons and 4 introns. IL-10 gene encodes a homodimer polypeptide with 178 amino acids in each subunit [6]. SNPs are located in the IL-10 gene promoter region, and one of the most important of them is -1082A/G (rs1800896) [7]. IL-10 polymorphism at position -1082A/G affects gene expression level so that a higher incidence of the G allele is linked to higher IL-10 expression, and higher IL-10 level is linked to increased susceptibility to some diseases [8].

Azeri population is one of Iran’s largest and most populous ethnic groups residing mostly in northwestern Iran. Like other Iranians, Azeri are Aryan and their language shifted to Turkish after Ilkhanate dynasty in northwestern Iran [9]. Due to the IL-10’s role and characteristics in susceptibility to various diseases and pathological processes as well as variations in its production level based on genetic polymorphism, it is necessary to study it in different populations. Therefore, in this study IL-10 polymorphism at -1082A/G position in the Azeri population of northwestern Iran was investigated.

Methods

Blood samples were collected from 254 non-kin Azeri healthy individuals living in East Azerbaijan province in Iran. Enrolled individuals were not infected to human immunodeficiency virus (HIV), hepatitis B, hepatitis C as well as tuberculosis based on their recent laboratory results provided on the questioner. They also had no cancer, or autoimmune diseases. Consent was obtained from all participants, and this study was approved by the Ethics Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1397.889). DNA extraction was performed through the described method by [10]. 150 μl TE buffer (10 M Tris–Cl, 1 mM EDTA, pH 8.0) was blended with 300 μl of buffy-coat through shaking. Then, 60 μl of 10% sodium dodecyl sulfate (SDS) and10 μl of 20 mg/ml of proteinase K (Cinnaclone, Iran) were blended with the solution and then incubated in 60 °C overnight. Later 100 μl of 5 M NaCl and 80 μl 10% cetyltrimethylammonium bromide (CTAB) + 0.7 M NaCl were added and vortexed, respectively. After 10 min of incubation at 65 °C, about 700 μl of chloroform/isoamyl (Merck, Germany) (24:1) was added and shaken for 20 s and then centrifuged for 8 min at 11,000 g. After centrifugation, the supernatant was transferred to a new microtube, and then, 2-propanol was added by the amount of 0.6 volume of solution and after mixing it was incubated at − 20 °C for 30 min. The suspension was then centrifuged for 15 min at 1200 g, and thereafter, 1 ml cold 70% ethanol was added to the solution for washing the DNA pellet. Finally, the DNA pellet was dissolved in 60 μl of distilled water and stockpiled at − 20 °C.

SNP A/G IL-10 -1082 (rs1800896) in the promoter section was genotyped by using the allele-specific-PCR method described previously [11]. The sequences of the primers used for genotyping include: (common primer) 5′-CAG TGCCAACTGAGA ATT TGG-3′, (primer A) 5′-ACT ACTAAGGCTTCTTTGGGA ACA-3′, (primer G) 5′-CTA CTAAGG CTT CTTTGGGAG-3′.

PCR was carried out in a total volume of 20 μl with approximately 100 ng genomic DNA, 100 μM dNTP, 0.5 μM of each primer, 50 mM Kcl, 20 Mm Tris–Cl (pH = 8.4), 1.5 mM MgCl2 and 1.25 units of recombinant Taq DNA polymerase (Cinnaclone, Iran). Cycling was carried out in Mastercycler gradient (Eppendorf, Germany) with the thermal cycling protocol of 94 °C for 7 min as initial denaturation, 35 cycles of 94 °C for 45 s, 60 °C for 45 s, 72 °C for 50 s and 72 °C for 7 min as final extension. After electrophoresing PCR products on 1.5% agarose gel, they were stained with ethidium bromide and analyzed under ultraviolet (UV) light. PCR products were 258 base pairs (bp) in size as compared to 100 bp DNA ladder plus (Fermentas, Lithuania). The q-square test was used to compare differences in IL-10 genotype and allele frequencies among different populations, and P value of < 0.05 was considered as significant level [12].

Results

IL-10 genotype and allele frequencies in healthy Azeri population in northwestern Iran at position -1082 A/G are shown in Table 1. Frequency percentages of AA, AG and GG genotypes were 37.4, 47.3 and 19.3%, respectively. The frequencies of A and G alleles frequencies were 59.1 and 40.9%, respectively. The frequency of IL-10 genotypes and alleles at -1082 A/G position from current sample population and other populations is observed in Tables 2 and 3. As can be seen, the genotypic and allele frequencies in this sample population are very similar to the genotypic frequency in Saudi Arabia (P ≥ 0.05), but it is significantly different from the genotypic frequency in East Asia and Ireland (P < 0.05).

Table 1 Genotype and allele frequency of IL-10(-1082) in Azeri population (Northwest of Iran)
Table 2 Frequency of IL-10 genotypes -1082 in healthy populations from various populations
Table 3 Frequency 0f IL-10 alleles -1082 in healthy populations from various populations

Discussion

Interleukins mediate intercellular contact in the immune system and are involved in inflammatory, tissue repair and host defense processes. Immunogenic loci influence susceptibility to a variety of diseases, especially inflammatory, neurological, infectious diseases and cancer, so that SNPs present in the promoter region of the IL-10 gene can affect expression, structure, quantity, function of IL-10 [13] and cause an imbalance between pro-inflammatory and anti-inflammatory interleukins. Distribution of alleles and SNP genotypes of IL-10 gene at -1082 position between healthy Azeri population and other healthy Asian populations as well as other European, African and American nations is compared in Tables 2 and 3. A significant difference in allelic and genotype distribution between healthy Azeri people and healthy Chinese population [8], Korean [14], Mexican [15], Polish [16], Northern Ireland [17] has been observed; however, there is only a significant difference in the distribution of alleles with healthy Bulgarian population, and no significant difference in genotypic distribution has been observed with Bulgarian population [18]. But there is a similarity with healthy people from Fars population of Iran [19], Saudi [20], Omani [17], Greek [21], Italian [22] and Egyptian [23]. In present study, AG genotype was the most abundant genotype which is greatly different with 6.6% frequency of AG genotype of Han population from China [8]. In terms of evolutionary trees, people of Azerbaijan are diverge from East Asian population and the genetic distance is at least 20,000 years [24]. According to the results of a study performed on Saudi Arabians, the prevalence of AA, AG and GG genotypes was 38.6, 42.7 and 18.7%, respectively, and is so similar to current study’s results [20]. It seems that due to the special interest of the Iranian people, especially Azeris in Prophet Mohammad (PBUH) and his descendants, a widespread migration of Prophet Mohammad’s descendants from Saudi Arabia and Iraq to Iran plateau, particularly northwestern Iran during Umayyad and Bani Abbas dynasties, had been occurred [25]. As a result of Sadat’s marriage to Azeris also, there has been a great genetic mixing which can be one of the reasons of the excessive similarity of IL-10 genotypes at position 1082A/G in Azeri and Saudi populations. Study of interleukins’ gene polymorphism along with mtDNA haplogroups can be a tool to study genetic evolutionary and correlations between populations to identify ethnic similarities and differences. The prevalence of AG genotype in the Azeri community was the highest, similar to that of North Africans, and this may be due to a genetic link between Azeri population of Iran and African people, which is consistent with African migration to other continents through the Iran plateau [26]. IL-10 is an interleukin that eliminates macrophages activation which makes it impossible to eradicate Mycobacterium tuberculosis within macrophages. While IFN-γ is effective against M. tuberculosis by stimulating macrophages [27], IL-10 renders the person more susceptible to tuberculosis. Eradicating tuberculosis in Iran, especially in northwestern region of Iran, is noteworthy because tuberculosis is an infectious disease that has caused problems with the development of its resistant type to drugs. G Allele, which is associated with high expression of IL-10, inhibits the immune system and predisposes people to tuberculosis, as Asgharzadeh et al. [11] discovered a substantial association between the incidence of tuberculosis and G allele at -1082 position. It appears that the GG genotype of the IL-10 gene at position -1082 plays a role in decreasing resistance to M. tuberculosis through increasing IL-10 expression and disrupting Th1/Th2 balance [28]. Since immune system defects predispose people to infectious diseases, the G allele at position 1082 of the IL-10 gene predisposes people to sepsis. Sepsis is a life-threatening condition caused by the immune system’s overreaction to microbial infections. To control the infection, body releases a huge amount of chemicals, which causes severe inflammation which ultimately spreads across the body, causing organ damage and even death in some cases [29]. As a result, identifying patients who are at a higher risk of developing sepsis may be preventative and life-saving.

Cancer is a disorder that is linked to an individual’s genetic polymorphism, and the prevalence of cancer is greater in people who do not have a good immune system. The immune system scans the body for cancer cells and kills them on a regular basis through cytotoxic T lymphocytes that sense cancer cell antigens with MHCI molecules. GG genotype and G allele raise IL-10 production and make people with this genotype more cancer-prone, so that the GG genotype in versus with AA genotype is a risk factor for gastric [30] and breast cancers [31]. It seems that IL-10 polymorphism can play a role in people’s susceptibility to various cancers, severity, clinical course and outcome of the disease.

The balance between pro-inflammatory and anti-inflammatory interleukins is essential for a proper immune response, and any dysregulation in this region can be associated with pathological conditions like autoimmune diseases. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which patient’s platelets are attacked by antibodies. The etiology of ITP is unclear, but it has been linked to both environmental and genetic factors, as AA genotype in -1082 IL-10 location predisposes individuals to ITP (p < 0.0013) [32], whereas other important autoimmune disorders, such as multiple sclerosis [16, 18] and rheumatoid arthritis (RA) [33], have no substantial association with IL-10 genotypes at location 1082. According to studies, people with the AA genotype and the A allele have a higher susceptibility to juvenile idiopathic arthritis (JIA) [34], asthma [35], ischemic stroke [36] and Alzheimer [37] than people with the GG genotype. Conversely, in comparison with the AA and AG genotypes, the GG genotype of the IL-10 -1082 predisposes individuals to hepatitis B virus (HBV), hepatitis C virus (HCV) [38], acute pancreatitis [13] and type 2 diabetes [39]. In contrast in a study, type 2 diabetes was more common in people with homozygous AA and GG genotypes and the AG genotype was more prevalent in controls. This can imply that high or low IL-10 is not beneficial to individuals, and balanced production is good for people [40]. Different results in various populations can be due to specific genetic variations, distant promoter elements, linkage disequilibrium with other loci and the presence of functional variants close to discussed polymorphism. Therefore, further studies should be performed on other IL-10 gene polymorphisms as well as gene polymorphisms in other interleukins in populations; also, their association with disease susceptibility should be investigated. As IL-10 inhibits IL-12 production and Th1 differentiation and prevents the recognition of viral infected and cancer cells through downregulating MHCI expression on cancer cells and antigen-presenting cells, it can be a target for cancer immunotherapy [41]. As a result, the use of an anti-IL-10 antibody may be useful for the treatment of viral infections and cancers with elevated IL-10 basic levels. Based on the above, it can be concluded that identifying interleukin genotypes in patients can be used to classify diseases and determine the optimal dose of drugs to cure diseases and minimize their side effects.

Conclusion

Polymorphism in IL-10 gene in the -1082 A/G affects its expression that the GG genotype is associated with high levels of IL-10 production. In the current study, AA and AG genotypes were more frequent than GG genotype. Low levels of IL-10 can be associated with susceptibility to some diseases. Results of the present study indicate similar polymorphism of IL-10 genotype with neighbor ethnicities in Middle East country. Based on patients backgrounds mentioned in their questioners, this polymorphism was associated with the susceptibility to asthma and Alzheimer in this population which are common in the region.

Availability of data and materials

The data supporting this research project are available at corresponding author upon request.

Abbreviations

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

IL:

Interleukin

ITP:

Idiopathic thrombocytopenic purpura

JIA:

Juvenile idiopathic arthritis

MHC II:

Major histocompatibility complex II

NK-cells:

Natural killer cells

RA:

Rheumatoid arthritis

SNP:

Single-nucleotide polymorphism

Th:

T helper

References

  1. Schirmer M, Kumar V, Netea MG, Xavier RJ (2018) The causes and consequences of variation in human cytokine production in health. Curr Opin Immunol 54:50–58. https://doi.org/10.1016/j.coi.2018.05.012

    Article  CAS  PubMed  Google Scholar 

  2. Rutz S, Ouyang W (2016) Regulation of Interleukin-10 Expression. Adv Exp Med Biol 941:89–116. https://doi.org/10.1007/978-94-024-0921-5_5

    Article  CAS  PubMed  Google Scholar 

  3. Saxena A, Khosraviani S, Noel S, Mohan D, Donner T, Hamad ARA (2015) Interleukin-10 paradox: a potent immunoregulatory cytokine that has been difficult to harness for immunotherapy. Cytokine 74(1):27–34

    Article  CAS  Google Scholar 

  4. Saraiva M, Vieira P, O’Garra A (2019) Biology and therapeutic potential of interleukin-10. J Exp Med. https://doi.org/10.1084/jem.20190418

    Article  PubMed Central  Google Scholar 

  5. Saraiva M, O’garra A (2010) The regulation of IL-10 production by immune cells. Nature Rev Immunol 10(3):170–181

    Article  CAS  Google Scholar 

  6. Mosser DM, Zhang X (2008) Interleukin-10: new perspectives on an old cytokine. Immunol Rev 226(1):205–218. https://doi.org/10.1111/j.1600-065X.2008.00706.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Suárez A, Castro P, Alonso R, Mozo L, Gutiérrez C (2003) Interindividual variations in constitutive interleukin-10 messenger RNA and protein levels and their association with genetic polymorphisms1. Transplantation 75(5):711–717. https://doi.org/10.1097/01.TP.0000055216.19866.9A

    Article  CAS  PubMed  Google Scholar 

  8. Guo J, He Y-H, Chen F, Jiang M-H, Gao S-P, Su Y, Shi G-L, Deng X-T, Zhu J-H, Pan M (2012) The A to G polymorphism at-1082 of the interleukin-10 gene is rare in the Han Chinese population. Mol Med Rep 6(4):894–896. https://doi.org/10.3892/mmr.2012.995

    Article  CAS  PubMed  Google Scholar 

  9. Asgharzadeh M, Samadi Kafil H, Ranjbar A, Rahimipour A, Najati K, Rahbani Nobar M (2011) Molecular diversity of mitochondrial DNA in Iranian Azeri ethnicities vis-à-vis other Azeris in Asia. Iran J Biotechnol 9(2):120–125

    Google Scholar 

  10. Asgharzadeh M, Kafil HS, Ebrahimzadeh M, Bohlouli A (2007) Mannose-binding lectin gene and promoter polymorphism and susceptibility to renal dysfunction in systemic lupus erythematosus. J Biol Sci 7(5):801–805

    Article  CAS  Google Scholar 

  11. Asgharzadeh M, Ghorghanlu S, Rashedi J, Poor BM, Khaki-Khatibi F, Moaddab SR, Samadi-Kafil H, Pourostadi M (2016) Association of promoter polymorphisms of interleukin-10 and interferon-gamma genes with tuberculosis in Azeri population of Iran. Iran J Allergy Asthma Immunol 15(3):167–173

    PubMed  Google Scholar 

  12. Kafil HS, Mobarez AM, Moghadam MF, Hashemi ZS, Yousefi M (2016) Gentamicin induces efaA expression and biofilm formation in Enterococcus faecalis. Microb Pathog 92:30–35

    Article  CAS  Google Scholar 

  13. Cai F, Cui N, Ma H, Wang X, Qiao G, Liu D (2015) Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population. Int J Clin Exp Pathol 8(11):15170–15176

    PubMed  PubMed Central  Google Scholar 

  14. Kim J, Cho YA, Choi IJ, Lee Y-S, Kim S-Y, Shin A, Cho S-J, Kook M-C, Nam JH, Ryu KW (2012) Effects of interleukin-10 polymorphisms, Helicobacter pylori infection, and smoking on the risk of noncardia gastric cancer. PLoS ONE 7(1):e29643. https://doi.org/10.1371/journal.pone.0029643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vázquez-Villamar M, Palafox-Sánchez C, Hernández-Bello J, Muñoz-Valle J, Valle Y, Cruz A, Alatorre-Meza A, Oregon-Romero E (2016) Frequency distribution of interleukin-10 haplotypes (-1082 A> G,-819 C> T, and-592 C> A) in a Mexican population. Genet Mol Res 15(4):1–11. https://doi.org/10.4238/gmr15048411

    Article  CAS  Google Scholar 

  16. Mirowska-Guzel D, Gromadzka G, Mach A, Czlonkowski A, Czlonkowska A (2011) Association of IL1A, IL1B, ILRN, IL6, IL10 and TNF-α polymorphisms with risk and clinical course of multiple sclerosis in a Polish population. J Neuroimmunol 236(1–2):87–92. https://doi.org/10.1016/j.jneuroim.2011.04.014

    Article  CAS  PubMed  Google Scholar 

  17. Meenagh A, Williams F, Ross OA, Patterson C, Gorodezky C, Hammond M, Leheny WA, Middleton D (2002) Frequency of cytokine polymorphisms in populations from western Europe, Africa, Asia, the Middle East and South America. Hum Immunol 63(11):1055–1061. https://doi.org/10.1016/S0198-8859(02)00440-8

    Article  CAS  PubMed  Google Scholar 

  18. Mihailova S, Ivanova M, Mihaylova A, Quin L, Mikova O, Naumova E (2005) Pro-and anti-inflammatory cytokine gene polymorphism profiles in Bulgarian multiple sclerosis patients. J Neuroimmunol 168(1–2):138–143. https://doi.org/10.1016/j.jneuroim.2005.06.020

    Article  CAS  PubMed  Google Scholar 

  19. Kurdistani ZK, Saberi S, Talebkhan Y, Oghalaie A, Esmaeili M, Mohajerani N, Bababeik M, Hassanpour P, Barani S, Farjaddoost A (2015) Distribution of cytokine gene single nucleotide polymorphisms among a multi-ethnic Iranian population. Adv Biomed Res. https://doi.org/10.4103/2277-9175.161809

    Article  PubMed  PubMed Central  Google Scholar 

  20. Alhamad EH, Cal JG, Shakoor Z, Almogren A (2013) Cytokine gene polymorphisms of TNFα, IL-6, IL-10, TGFβ and IFNγ in the Saudi population. Br J Biomed Sci 70(3):104–109. https://doi.org/10.1080/09674845.2013.11669944

    Article  CAS  PubMed  Google Scholar 

  21. Costeas P, Koumas L, Koumouli A, Kyriakou-Giantsiou A, Papaloizou A (2003) Cytokine polymorphism frequencies in the Greek Cypriot population. Eur J Immunogenet 30(5):341–343. https://doi.org/10.1046/j.1365-2370.2003.00413.x

    Article  CAS  PubMed  Google Scholar 

  22. Uboldi de Capei M, Dametto E, Fasano M, Rendine S, Curtoni E (2003) Genotyping for cytokine polymorphisms: allele frequencies in the Italian population. Eur J Immunogenet 30(1):5–10. https://doi.org/10.1046/j.1365-2370.2003.00361.x

    Article  CAS  PubMed  Google Scholar 

  23. Talaat RM, Dondeti MF, El-Shenawy SZ, Khamiss OA (2014) Association between IL-10 gene promoter polymorphism and hepatitis B viral infection in an Egyptian population. Biochem Genet 52(9–10):387–402. https://doi.org/10.1007/s10528-014-9655-8

    Article  CAS  PubMed  Google Scholar 

  24. Nei M, Saitou N (1986) Genetic relationship of human populations and ethnic differences in reaction to drugs and food. Prog Clin Biol Res 214:21–37

    CAS  PubMed  Google Scholar 

  25. Rafiee M-R, Sokhansanj A, Naghizadeh M-A, Farazmand A (2009) Analysis of Y-chromosomal short tandem repeat (STR) polymorphism in an Iranian Sadat population. Russ J Genet 45(8):969–973. https://doi.org/10.1134/S1022795409080110

    Article  CAS  Google Scholar 

  26. Ingman M, Kaessmann H, Pääbo S, Gyllensten U (2000) Mitochondrial genome variation and the origin of modern humans. Nature 408(6813):708–713

    Article  CAS  Google Scholar 

  27. Asgharzadeh M, Fadaee M, Mahdavipoor B, Sheykhsaran E, Rashedi J, Pourostadi M, Asgharzadeh V, Vegari A, Kafil HS (2020) Polymorphism of the IFN-ɣ gene in the Azeri population of Iran. Gene Reports 19:100596. https://doi.org/10.1016/j.genrep.2020.100596

    Article  CAS  Google Scholar 

  28. Ates Ö, Musellim B, Ongen G, Topal-Sarıkaya A (2008) Interleukin-10 and tumor necrosis factor-α gene polymorphisms in tuberculosis. J Clin Immunol 28(3):232–236. https://doi.org/10.1007/s10875-007-9155-2

    Article  CAS  PubMed  Google Scholar 

  29. Ouyang L, Lv Y-D, Hou C, Wu G-B, He Z-H (2013) Quantitative analysis of the association between interleukin-10 1082A/G polymorphism and susceptibility to sepsis. Mol Biol Rep 40(7):4327–4332

    Article  CAS  Google Scholar 

  30. Namazi A, Forat-Yazdi M, Jafari M, Farahnak S, Nasiri R, Foroughi E, Abolbaghaei SM, Neamatzadeh H (2018) Association of interleukin-10-1082 A/G (rs1800896) polymorphism with susceptibility to gastric cancer: meta-analysis of 6.101 cases and 8.557 controls. Arq Gastroenterol 55(1):33–40. https://doi.org/10.1590/s0004-2803.201800000-18

    Article  PubMed  Google Scholar 

  31. Zhu Z, Liu J-B, Liu X, Qian L (2020) Association of interleukin 10 rs1800896 polymorphism with susceptibility to breast cancer: a meta-analysis. J Int Med Res 48(4):0300060520904863. https://doi.org/10.1177/0300060520904863

    Article  CAS  PubMed Central  Google Scholar 

  32. Thadani J, Dwivedi M, Mansuri MS, Singh M, Bhatwadekar S, Barot B, Begum R, Salunke S (2018) Role of TNF −308 G/A, TNFβ +252 A/G and IL10 −592 C/A and −1082 G/A SNPs in pathogenesis of Immune Thrombocytopenia Purpura in population of Gujarat, India. Gene Reports 12:304–309. https://doi.org/10.1016/j.genrep.2018.07.001

    Article  Google Scholar 

  33. Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S (2010) Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int 30(9):1211–1217. https://doi.org/10.1007/s00296-009-1131-0

    Article  CAS  PubMed  Google Scholar 

  34. Fathy MM, Elsaadany HF, Ali YF, Farghaly MA, Hamed ME, Ibrahim HE, Noah MA, Allah MA, Elashkar SS, Abdelsalam NI (2017) Association of IL-10 gene polymorphisms and susceptibility to Juvenile Idiopathic Arthritis in Egyptian children and adolescents: a case-control study. Ital J Pediatr 43(1):1–8. https://doi.org/10.1186/s13052-017-0328-1

    Article  CAS  Google Scholar 

  35. Zheng X-Y, Guan W-J, Mao C, Chen H-F, Ding H, Zheng J-P, Hu T-T, Luo M-H, Huang Y-H, Chen Q (2014) Interleukin-10 promoter 1082/− 819/− 592 polymorphisms are associated with asthma susceptibility in Asians and atopic asthma: a meta-analysis. Lung 192(1):65–73. https://doi.org/10.1007/s00408-013-9519-8

    Article  CAS  PubMed  Google Scholar 

  36. Jin J, Li W, Peng L, Chen J, Li R, Wu P, Tan S (2014) Relationship between interleukin-10− 1082A/G polymorphism and risk of ischemic stroke: a meta-analysis. PLoS ONE 9(4):e94631

    Article  Google Scholar 

  37. Zhang Y, Zhang J, Tian C, Xiao Y, Li X, He C, Huang J, Fan H (2011) The −1082G/A polymorphism in IL-10 gene is associated with risk of Alzheimer’s disease: a meta-analysis. J Neurol Sci 303(1–2):133–138. https://doi.org/10.1016/j.jns.2010.12.005

    Article  CAS  PubMed  Google Scholar 

  38. Zhang Y, Chen L, Chen H (2020) Associations between polymorphisms in IL-10 gene and the risk of viral hepatitis: a meta-analysis. Gut Pathog 12(1):1–10. https://doi.org/10.1186/s13099-020-00372-7

    Article  CAS  Google Scholar 

  39. Tarabay M, Elshazli R, Settin A (2016) African vs. Caucasian and Asian difference for the association of interleukin-10 promotor polymorphisms with type 2 diabetes mellitus (a meta-analysis study). Meta Gene 9:10–17. https://doi.org/10.1016/j.mgene.2016.02.006

    Article  PubMed  PubMed Central  Google Scholar 

  40. Naz S, Shafique N, Sharif S, Manzoor F, Safi SZ, Firasat S, Kaul H (2020) Association of interleukin 10 (IL-10) gene with type 2 diabetes mellitus by single nucleotide polymorphism of its promotor region G/A 1082. Crit Rev™ Eukaryot Gene Expr. https://doi.org/10.1615/CritRevEukaryotGeneExpr.2020030714

    Article  Google Scholar 

  41. Wang X, Wong K, Ouyang W, Rutz S (2019) Targeting IL-10 family cytokines for the treatment of human diseases. Cold Spring Harb Perspect Biol 11(2):a028548

    Article  CAS  Google Scholar 

  42. Luomala M, Lehtimäki T, Huhtala H, Ukkonen M, Koivula T, Hurme M, Elovaara I (2003) Promoter polymorphism of IL-10 and severity of multiple sclerosis. Acta Neurol Scand 108(6):396–400

    Article  CAS  Google Scholar 

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Acknowledgements

We thank DARC staff for all their support and collaborations.

Funding

This study was supported by the Para-medicine faculty with Grant Number 61930, Tabriz University of Medical Sciences.

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Authors

Contributions

MA contributed to study design, sample collection, molecular analysis, data analysis, manuscript preparation and final proof. ZT was involved in sample collection, molecular analysis and final proof. VA contributed to sample collection and final proof. BM was involved in study design, data analysis and final proof. JR contributed to study design, manuscript preparation and final proof. BM was involved in sample collection, manuscript preparation and final proof. MP contributed to molecular analysis and final proof. AV was involved in sample collection, data analysis and final proof. ASV contributed to molecular analysis, manuscript preparation and final proof. ST was involved in study design, data analysis and final proof. HSK contributed to study design, molecular analysis, data analysis, manuscript preparation and final proof. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hossein Samadi Kafil.

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This study was approved by local ethic committee with reference number 61930. 1398.12.11. All process was done according to Helsinki declaration. All consent forms are available, and study data were collected as blind forms with no identity from patients.

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Asgharzadeh, M., Taghinejad, Z., Asgharzadeh, V. et al. Polymorphism of the IL-10 gene in Azeri population of Iran. Egypt J Med Hum Genet 23, 113 (2022). https://doi.org/10.1186/s43042-022-00324-7

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  • DOI: https://doi.org/10.1186/s43042-022-00324-7

Keywords

  • IL-10
  • Genotype
  • Single-nucleotide polymorphisms
  • Iranian Azeri population