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Background   The vitamin D receptor ( VDR ) gene regulates insulin secretion from the pancreas and acts as a mediator of the immune response through vitamin D. Polymorphism in  VDR  causes alterations in the functioning of vitamin D, leading to type 1 diabetes (T1D) predisposition. The aim of the present study was to determine  VDR  gene polymorphism in association with T1D in Pakistanis.Methods   The association was evaluated by selecting rs2228570 ( FokΙ ), rs7975232 ( Apa Ι), and rs731236 ( Taq Ι) polymorphic sites in 102 patients and 100 controls. Genotypes were identified by DNA sequencing and PCR-RFLP.Results   The allelic and genotypic frequencies of  FokΙ  and  Apa I were significantly associated with T1D ( p  < 0.001) development. At the  Fok Ι site, tryptophan was replaced with arginine due to polymorphism. A novel SNP (GeneBank acc number KT280406) was identified through the sequencing of intron 8, 62 bp downstream from the  Apa I polymorphic site, and significantly associated with T1D development. The  TaqΙ  did not depict any association with T1D at the allelic or genotypic level ( p  > 0.05). CCGC, CCGG, CCTC, and CCTG haplotypes were significantly associated with disease development ( p  < 0.05). However, CTGG haplotype was protective towards T1D ( p  < 0.01).Conclusion    VDR  polymorphisms were identified as susceptible regions for T1D development in the Pakistani population.

Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis