Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis

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 (ApaΙ), and rs731236 (TaqΙ) 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 ApaI were significantly associated with T1D (p < 0.001) development. At the FokΙ 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 ApaI 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 and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis

“…Finally, 24 case-control studies with 2436 cases and 4074 controls were identified eligible for quantitative synthesis of the association between ApaI polymorphism and T1DM risk. Overall, 10 studies were conducted in Europe [ 15 , 35 , 36 , 38 , 41 , 44 , 59 , 60 ], 10 studies were in Asia [ 42 , 46 , 48 , 54 , 55 , 57 , 58 , 62 – 64 ], 2 studies in Africa [ 52 , 65 ] and one study each was in Australia [ 50 ] and America [ 61 ]. Because of limited number of studies performed in Australia, America and Africa these studies were excluded from subgroup analysis.…”

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

“…The pathogenetic role of vitamin D in T1DM onset is debated. The Type 1 Diabetes Genetic Consortium, which genotypically characterized 38 single nucleotide polymorphisms (SNPs) in more than 1500 families with T1DM, did not observe correlations between SNPs in the VDR and T1DM [138], even if associations between some VDR polymorphisms (BsmI, FokI, TaqI, ApaI) and T1DM have been pinpointed in several population studies [139][140][141][142][143][144][145][146][147][148]. In 2017, Sahin OA et al [149] published a meta-analysis, with the aim to evaluate the relationship between ApaI, BsmI, FokI, and TaqI polymorphisms of VDR and T1DM in children.…”

Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-analysis based on 40 case–control studies

“…Overall, 29 case-control studies with cases and 5578 controls were analyzed for assessment of FokI polymorphism and T1DM risk. Of 29 studies, 15 studies were conducted in European countries [15,[34][35][36][37][38][39][40][41][42][43][44], 9 studies were in Asian countries [45][46][47][48][49][50][51][52][53], 3 studies were in African population [54][55][56] and eventually one study in Australia [57] and one study in American population [58]. Among studies were performed in Europe, Audi et al [37] conducted an association study in different city of Spain (Barcelona and Navarra) and reported all data separately including genotype and allele frequency; thus we considered each population as a separate study.…”