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 is an anti-inflammatory molecule and has a role in prevention of arthritis development. Biologically active form 1, 25(OH)2D3 of vitamin D can only exert its action after binding its definite vitamin D receptor encoded by VDR gene. VDR gene polymorphism leads to dysfunctioning of 1, 25(OH)2D3 ultimately disease onset. The purpose of current study was to evaluate the effect of vitamin D level and VDR gene polymorphism on rheumatoid arthritis and osteoarthritis. Blood samples were collected from case and control after taking written consent. Serum was separated and vitamin D level as determined from each sample by ELISA. DNA was extracted from each blood sample and amplified by using gene specific primers. Genotyping was performed by Sangers sequencing and PCR-RFLP technique. It was found that vitamin D level was not significantly different among patients and controls. The rs10735810, rs1544410, rs7975232, and rs731236 were associated with the onset of arthritis at both allelic and genotypic level (p < 0.01). Nucleotide change on rs10735810 site leads to change of tryptophan with arginine. The frequencies of haplotype CGAT, CGGA, CGGT, CTAA, CTAT, TGAA, TGAT, TGGA, and TTGA were higher in patients and act as risk factors of RA onset, whereas haplotypes CGAT, CGAT, CGGT, CTGA, TGAT, TGGA, TTAA, and TTGA were associated with OA onset. In conclusion, serum vitamin D level may be normal among arthritis patients but polymorphism on VDR gene restricts vitamin D to perform its anti-inflammatory function by altering the 1, 25(OH)2 D3 binding sites.

A number of genes are known to be involved in glucose homeostasis. Mutations and polymorphisms in candidate genes may effect insulin production, action or resistance. This study was designed to report the association of genetic polymorphism with the type 2 diabetes (T2D) in Pakistani population. A total of 458 subjects (case n=288, control n=170) participated in the study. Nine single nucleotide polymorphisms were investigated in genes IDE (rs6583813 C>T, rs7910977 C>T), POU2F1 (rs3767434 A>T, rs10918682 A>T, rs2146727 A>G), WFS1 (rs734312 A>G), PON1 (rs854560 T>A), IL1α (rs1800587 C>T) and IL1β (rs1143634 C>T). Genotyping was performed by DNA sequencing after nested polymerase chain reaction of targeted regions. Results indicated that rs7910977 in IDE showed significant association with the development of T2D [P=0.012, OR 1.677 (95% CI 1.112-2.438)]. The rs10918682 in POU2F1 was associated with T2D [P<0.001, OR 3.606 (95% CI 2.165-6.005)]. The rs854560 in PON1 was associated with incidences of T2D and increased the risk of cardiovascular complications [P=0.031, OR 0.663 (95% CI 0.455-0.965)] in diabetics. The rs734312 from WFS1 gene was associated with diabetes at genotype level (P<0.01). Haplotype analysis of rs1800587-rs1143634 depicted CC haplotype increased the susceptibility to diabetes (P<0.05). Haplotype GAA from rs2146727-10918682-rs3767434 was protective against diabetes (P<0.01) and GGA exhibited the association with T2D (P<0.01). Haplotype CT from rs6583813-rs7910977 was protective against diabetes (P=0.02). Our study provided evidence to IDE, PON1, WFS1, POU2F1, IL1α and IL1β associated with T2D in Pakistanis.