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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 (Fok?), rs7975232 (Apa?), and rs731236 (Taq?) polymorphic sites in 102 patients and 100 controls. Genotypes were identified by DNA sequencing and PCR-RFLP. Results:The allelic and genotypic frequencies of Fok? and ApaI were significantly associated with T1D (p < 0.001) development. At the Fok? 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 Taq? 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.

SUBMITTER: Mukhtar M

PROVIDER: S-EPMC5733195 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis.

Mukhtar Maryam M Batool Andleeb A Wajid Abdul A Qayyum Iram I

International journal of genomics 20171203

<h4>Background</h4>The vitamin D receptor (<i>VDR</i>) gene regulates insulin secretion from the pancreas and acts as a mediator of the immune response through vitamin D. Polymorphism in <i>VDR</i> causes alterations in the functioning of vitamin D, leading to type 1 diabetes (T1D) predisposition. The aim of the present study was to determine <i>VDR</i> gene polymorphism in association with T1D in Pakistanis.<h4>Methods</h4>The association was evaluated by selecting rs2228570 (<i>FokΙ</i>), rs79 ...[more]

PMID: 29333433

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Project description:BACKGROUND:The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility. METHODS:The genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays. RESULTS:Statistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C?>?T, rs10735810 and TaqI, C?>?T, rs731236) between T1DM patients and controls (P?<?0.0001). In both, the frequency of variant alleles was considerably high in T1DM than in the controls. In contrast, the VDR gene ApaI (G?>?T, rs7975232) and BsmI (A?>?G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and?>?6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes. CONCLUSIONS:Our results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.

Project description:Introduction:Vitamin D receptor (VDR) plays an important role in activating the immune response against various infectious agents. It is known that the active metabolite of ligand receptor Vitamin D (1,25 - dihydroxyvitamin D) is encoded by VDR and helps mononuclear phagocytes to suppress the intracellular growth of M. tuberculosis. The VDR gene harbors approximately 200 polymorphisms, some of which are linked to differences in receptor Vitamin D uptake and therefore can be considered as candidate disease risk variants. The relation between VDR gene polymorphisms and susceptibility to TB has been studied in different populations. There is not a great deal of information regarding the association of these SNPs with TB risk in the Kazakh population. The four most commonly investigated VDR polymorphisms in association with different diseases, including susceptibility to tuberculosis, are located in exon 2 (rs2228570 or FokI), intron 8 (rs1544410 or BsmI and rs7975232 or ApaI), and exon 9 (rs731236 or TaqI). The aim of our study was to determine whether these four VDR gene single nucleotide polymorphisms were associated with TB and whether they were a risk for the development of TB in the Kazakh Population in Almaty city and Almaty area. Methods:This study was a hospital-based case-control analysis of 283 individuals (99 TB patients and 184 healthy controls). Genotyping was performed by Taqman SNP allelic discrimination using commercial TaqMan SNP Genotyping assays. Statistical analysis was conducted using SPSS Version 19.0 software. Results:Genotype frequencies for the Kazakh population are close to world (HapMap) data on Asian populations. FokI and ApaI polymorphisms genotypes tend to be associated with TB risk under the co-dominant model [OR=1.18; 95%CI: (0.68, 2.07), p=0.15] for FokI and [OR=1.33; 95%CI: (0.61, 2.91), p=0.6] for ApaI. No significant association between the disease and TaqI, BsmI genotypes was observed. Conclusions:In summary, we explored potential associations between SNPs in the VDR (FokI, ApaI) gene and susceptibility to tuberculosis in the Kazakh Population, which requires further detailed analysis with a larger sample size and greater geographic diversity including other regions of Kazakhstan.

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Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis.

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Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis.

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