Association of Vitamin D Deficiency and Vitamin D Receptor Gene Polymorphisms with Type 1 Diabetes Risk: A South Indian Familial Study

Objective: Vitamin D is a potent immune modulator and is associated with autoimmune diseases, including type 1 diabetes (T1D).The vitamin D levels and its receptor gene polymorphisms together in T1D are not yet investigated in the South Indian population.The present study focused on exploring the significance of vitamin D levels and vitamin D receptor (VDR) gene polymorphisms with the risk of developing T1D in the South Indian population.Methods: Patients with T1D and unaffected first-degree relatives (FDRs) were included in this study.Genotyping of VDR polymorphisms at four different loci (FokI-F/f, BsmI-B/b, TaqI-T/t, and ApaI-A/a) was assessed through the amplification refractive mutation systempolymerase chain reaction method.Serum vitamin D levels were measured in 98 T1D patients and 75 age-and sex-matched siblings.Results: A total of 120 patients with T1D and 214 FDRs were included.Vitamin D deficiency (VDD) was observed in a higher proportion of T1D patients than in controls (52% vs. 32%; p<0.03).The frequency of the FokI-FF genotype was significantly higher [odds ratio (OR)=1.66;p<0.03] in T1D patients conferring a susceptible association with the disease.Nevertheless, the increased frequency of heterozygous Ff genotype (OR=0.57;p<0.02) among controls may confer a protective association with T1D.Furthermore, the transmission disequilibrium test revealed over-transmission of ApaI-A (T: U=15/5; p<0.006) and BsmI-B alleles (T: U=17/5; p<0.01) and under-transmission of BsmI-b/ApaI-a/TaqI-T haplotype (T: U=5.4/14.4;p=0.04) from parents to T1D patients. Conclusion:The present study concludes that VDD is the major contributing risk factor to T1D development in the South Indian population.Furthermore, the FokI-FF genotype, BsmI-B, and ApaI-A alleles were positively associated with T1D.In contrast, the FokI-Ff genotype and BsmI-b/ApaI-a/TaqI-T haplotype were negatively associated with T1D.