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. 2017:2017:4171254.
doi: 10.1155/2017/4171254. Epub 2017 Dec 3.

Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis

Maryam Mukhtar  1 , Andleeb Batool  1 , Abdul Wajid  2 , Iram Qayyum  1
Affiliations

Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis

Maryam Mukhtar et al. Int J Genomics. 2017.

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.

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Figures

Figure 1
Figure 1
FokΙ digestion (SNP C/T) in exon 2: Restriction site presence is designated by “f,” and absence is designated by “F.” ff (CC), for example, a 196 bp and 69 bp; Ff (CT), for example, 265 bp, 196 bp, and 69 bp, bands; FF (TT), for example, 196 bp and 69 bp bands.
Figure 2
Figure 2
Representation of novel mutation identified at intron 8. (a) Patient genotype (GC) and (b) control genotype (GG).
Figure 3
Figure 3
Location and map of linkage disequilibrium (LD) in SNPs at VDR gene are presented. The SNP numbers are indicated at the top of haploview. (a) LD = D/ and (b) LD coefficient. Red = linkage is highly significant, pink = significant, and white = not significant (decrease in color sharpness indicated reduce chances of disease transfer to next generation).
See this image and copyright information in PMC

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