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

BACKGROUND: Vitamin D is a potent immune modulator and is associated with autoimmune diseases, predominantly Type 1 diabetes (T1D). Vitamin D status and its receptor gene polymorphisms in T1D are not yet investigated in the South Indian population.

OBJECTIVE: The present study focuses on exploring the significance of vitamin D levels and Vitamin D receptor (VDR) gene polymorphisms with the risk of T1D in the South Indian population.

METHODS: A total of 120 T1D patients along with 214 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 ARMS-PCR method. Serum vitamin D levels were measured in 98 T1D patients and 75 age and sex-matched siblings by the ELISA method.

RESULTS: 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 (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. Further, the TDT analysis 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 a major contributing risk factor to T1D development in the South Indian population. Furthermore, the FokI-FF genotype, BsmI-B, and ApaI-A alleles are positively associated with T1D risk. Whereas, the FokI-Ff genotype and BsmI-b/ApaI-a/TaqI-T haplotype are negatively associated with the disease.