Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis. (3rd December 2017) - Mukhtar, Maryam
Abstract : 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.