Vitamin D deficiency has remained a global problem over the past 25 years. Due to polymorphic VDR expression, an individual may obtain little or no vitamin-D-related advantages even if his/her vitamin D levels are normal. Multiple clinical investigations have linked VDR gene polymorphisms, including FokI, ApaI, TaqI, and BsmI, to obesity and metabolic syndrome. Genetic and immunological investigations have been conducted on obese individuals to explore the mechanisms underlying VDR polymorphism (BsmI) in the etiology of obesity .
Regarding the VDR gene polymorphism BsmI, we found that 24 participants had the Bb genotype, and six had the BB genotype, indicating that the “b” allele was more prevalent among obese participants.
Vitamin D levels and BsmI gene polymorphism also showed a correlation. In Group I with normal vitamin D levels, all the seven subjects with insufficient vitamin D levels had the Bb genotype (six Bb genotype carriers and one BB genotype carrier), whereas in Group II with deficient vitamin D levels, all the five participants were Bb genotype carriers. In contrast, we detected 13 Bb genotype carriers and 5 BB genotype carriers in Group II with low vitamin D levels. The incidence of BB genotype was higher among vitamin-D-deficient individuals, and Bb genotype carriers were more common among obese participants than BB genotype carriers. Nevertheless, the findings were not statistically significant.
In some populations, VDR and its genetic variations are known to influence the risk of obesity. Although the significance of low vitamin D levels in the development of obesity remains uncertain, some studies have shed light on the link between the two conditions. According to Kull et al., obese people are less exposed to sunlight compared with nonobese adults because of reduced physical activity or clothing patterns that impair cutaneous vitamin D production . Another in vitro study demonstrated that deficient vitamin D levels in obese subjects are due to adipose tissue sequestration of this vitamin .
Another notion is that due to hepatic steatosis, vitamin D production by the liver is reduced in obese people. Moreover, higher levels of circulating leptin and interleukin 6, which are largely produced by adipose tissue, may impede vitamin D production through their receptors .
Vitamin D deficiency also causes impaired insulin sensitivity, increased fat mass, and accelerated lipogenesis .
Human subcutaneous adipose tissue, visceral adipose tissue, and breast adipocytes have been found to express VDR. Vitamin D can both control and be regulated by adipose tissue. Human adipocytes have been shown to exhibit VDR, 25-hydroxyvitamin D 1-hydroxylase genes, and the 24-hydroxylase enzyme .
Ruiz-Ojeda et al. reported about relationships with VDR polymorphisms that could be attributed to either a major effect of vitamin D on adipocyte differentiation and metabolism or an indirect effect via the modulation of insulin secretion . Vitamin D is known to suppress gluconeogenesis, enhance HDL cholesterol levels, improve the adipokine profile, and increase leptin levels in adipose tissue. The active metabolite of vitamin D affects pancreatic beta cells, changing insulin sensitivity and improving the lipid profile. Consequently, insulin receptor expression increases, and insulin sensitivity improves. Vitamin D is required for reducing the risk of type 2 diabetes and altering the adipokine secretion profile .
Although we found no statistical significance between VDR gene polymorphism and BMI, waist–hip ratio (WHR), or other InBody bioelectrical impedance parameters in our study concerning the association between VDR gene polymorphism and obesity development, we did observe a prevalence of Bb genotype carriers among obese male students. Because the BsmI gene is found in the introns of VDR gene, it may have an impact on gene expression, mRNA stability, and protein translation efficiency . Thus, according to Chen et al., SNPs such as the “b” allele in BsmI, which can result in reduced VDR mRNA and protein expressions, may be related to an increased risk of developing obesity .
Bagheri et al. found that BsmI polymorphism was not associated with obesity risk in the Iranian population . However, another study showed that the “b” allele of the BsmI marker was more common among obese Saudi Arabians .
The effects of VDR polymorphism on body size were also explored, and it was found that the “b” allele in BsmI was linked to obesity in Caucasian women .
There was no relationship between vitamin D levels and the InBody bioelectrical impedance characteristics in our study. Other studies on people with vitamin D deficiency and obesity also showed no relationship between vitamin D levels and visceral fat, which supports our findings . In two clinical trials of obese people, no significant changes were detected in body weight, WHR, or vitamin D levels ,23.
Our findings support those of Vimaleswaran et al., who found no relationship between VDR, waist circumference, BMI, and other obesity-related parameters. Tworowska-Bardziska et al. also validated this conclusion in their study on a Polish cohort 25.
However, our findings were in contrast to the study of Bienertová-Vašků et al. conducted on 882 Central European Caucasian individuals, in which weight, height, BMI, lean body mass, fat mass, body fat, waist and hip circumference, waist–hip ratio, and skinfold thickness were measured, and the VDR BsmI gene polymorphism was investigated, reporting a relationship with waist circumference . The cross-sectional study of Karonova et al. on 697 participants supports our findings. They evaluated the VDR gene polymorphism rs1544410 (BsmI), serum vitamin D concentration, and anthropometric measurements and reported no significant relationship between the VDR SNP rs1544410 (BsmI), serum vitamin D concentration, anthropometric characteristics, and metabolic syndrome risk .
Zhao et al. conducted a study on Northern Chinese population and observed a strong relationship between the BsmI VDR gene polymorphism and metabolic syndrome, which is in contrast to our findings. They found that the BB genotype and B allele were risk factors for metabolic syndrome. The role of the bb genotype was unknown due to its rarity .
Marozik et al. predicted that the level of VDR mRNA was dramatically higher in BB genotype carriers than in bb genotype carriers, which could explain our study finding regarding the predominance of BB genotype with vitamin D deficiency in obese male students. VDR receptor expression was higher among BB genotype carriers, resulting in enhanced vitamin D catabolism. A possible mechanism is that a variation in VDR receptor activation alters vitamin-D-mediated gene expression .
Our findings, which were consistent with those of El-Hoseiny et al., showed that vitamin D insufficiency was more common among BB genotype carriers (66.7%) than among Bb and bb genotype carriers (33.3%) . El-Edel et al. also found that patients with beta thalassemia with the BB genotype had significantly lower bone mineral density than those with the bb or Bb genotype .
We suggest that people with VDR genotypes have a wide range of serum vitamin D concentrations, which further suggests that vitamin D supplementation may not be appropriate for everyone. The association between genetic variations and vitamin D status should also be further investigated.
Vitamin D exerts functions such as antioxidation, free radical scavenging, and neuroprotection. Therefore, a deficiency in this vitamin plays an important role in the initiation and progression of hypertension. The renin–angiotensin system, which has been reported to regulate blood pressure through vitamin D, is well known to be at the center of hypertension regulation .
Vitamin D acts on VDR, which is found on B cells, T cells, dendritic cells, and macrophages, and possesses immunomodulatory capabilities. VDR-expressing eosinophils have a longer lifespan .
In the present study, we detected a statistically significant difference between BB and Bb genotype carriers in terms of eosinophil count, with Bb genotype carriers having a higher mean value than BB genotype carriers. This finding may have implications for VDR function and, therefore, the role of vitamin D in immunomodulation. Further research is required to understand better about this enigmatic association.
In contrast to the study of De Groot et al., Filho et al. reported that lower serum vitamin D levels were related to an increased blood eosinophil count  .
We observed a statistically significant relationship between HbA1c levels and BsmI gene polymorphisms and an increase in mean value in Bb genotype carriers compared with BB genotype carriers. According to Ezhilarasi et al., BsmI SNPs in the VDR gene are associated with a range of biochemical markers, including BMI, fasting glucose, HbA1c, and lipid profile . The study of Mackawy and Badawi  also supports our findings.
The primary strength of our study was the fact that it is a pilot investigation, and moreover, all candidates were of same age and gender, which helps reduce gender disparities in various parameters. This study is also a continuation of a large project attempting to determine the effect of vitamin D and VDR gene polymorphism on obesity and its negative outcomes on various scales. In addition, laboratory tests were conducted by trained specialists, and the individuals provided detailed physical and medical history.
However, the small sample size may be the most significant limitation in our study. Moreover, we investigated only one VDR SNP, and hence, further research on other VDR gene polymorphisms is necessary to widen our study scope and understand better about the complex relationship between VDR gene polymorphism and obesity.