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.
Genetic polymorphismsof MYOCalter the myocilin protein,which leads to disruption of thenormal regulation of intraocular pressure (IOP) that ultimately causes glaucoma.Theaim of the present study was to identify the polymorphism in exon 3 of the MYOC gene of theglaucoma patients in Lahore, Pakistan. We conducted a case-control study with 100 patients and 100 controls subjects. We extracted DNA from blood samples,amplified the target DNA fragmentby PCR, and identifiedpolymorphisms through sequencing. We observed that the allelic and genotypic frequencies of rs74315341 and rs879255525 were associated with glaucoma in our patient population. The polymorphism atrs74315341 led to the substitutionof serine for arginine,whereas the polymorphism at rs879255525 led to the substitution ofasparagine for lysine. The haplotype was associated with disease onset, whereas the haplotype was protective against disease development. In conclusion, weidentified MYOC gene polymorphisms in susceptible regions that were associated withglaucoma onset among the Lahore patient population.This is the first report to identify a novel mutation in rs879255525 in exon 3 of the MYOC genethat is associated withglaucoma.
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