TT genotype at rs۴۵۱۶۰۳۵ is associated with increased susceptibility to osteoporosis in South-Eastern Iranian people

Backgrounds: Osteoporosis is a wide-spread disease with a major impact on families andsociety. In addition to calcium and vitamin D deficiency, genetic factors also play a crucial rolein the development of this disease. Any reduction in the function of Vitamin D receptor (VDR)can lead to osteoporosis.Materials and Methods: In this study, we selected six SNPs (rs۱۱۵۶۸۸۲۰, rs۴۵۱۶۰۳۵,rs۲۲۲۸۵۷۰, rs۱۵۴۴۴۱۰, rs۷۹۷۵۲۳۲ and rs۷۳۱۲۳۶) in the VDR gene. The genotype of SNPs wasstudied by PCR-RFLP, T-ARMS-PCR and sequencing in two groups of osteoporotic patients (n= ۴۰) and control (n = ۴۲). The levels of calcium and vitamin D۳ in patient’s blood were alsomeasured. The association between the SNPs and the incidence of osteoporosis was measured bycalculating odds ratio (OR).Results: Despite having osteoporosis, none of the patients had calcium or severe vitamin D۳deficiency. The results of PCR showed that among the six SNPs, only the TT genotype at thers۴۵۱۶۰۳۵ locus significantly increased the chance of disease by ۳.۰۶۱ times (P value = ۰.۰۰۷).The presence of C allele at this position adds ۵۰ amino acids to the protein and produces thelonger VDRB۱ variant with ۴۷۷ residues. The response to the vitamin D and the activity ofVDRB۱ is more than the ordinary variant, VDRA which has ۴۲۷ residues.Conclusion: Collectively, our data indicates the presence of VDRA variant in peoples whichhave TT genotype could be the reason for lesser activity of VDR and their greater susceptibilityto osteoporosis.

کلیدواژه ها:

Osteoporosis ، Single nucleotide polymorphism ، VDR ، rs۴۵۱۶۰۳۵ ، Odds ratio