A Candidate Gene Association Study of Bone Mineral Density in an Iranian Population

Abstract

The genetic epidemiology of variation in bone mineral density (BMD) and osteoporosis is not well studied in Iranian populations and needs more research. We report a candidate gene association study of BMD variation in a healthy cross-sectional study of 501 males and females sampled from the Iranian Multi-Centre Osteoporosis Study, Shiraz, Iran. We selected to study the association with 21 single nucleotide polymorphisms (SNPs) located in the 7 candidate genes LRP5, RANK, RANKL, OPG, P2RX7, VDR, and ESR1. BMD was measured at the three sites L2–L4, neck of femur, and total hip. Association between BMD and each SNP was assessed using multiple linear regression assuming an allele dose (additive effect) on BMD (adjusted for age and sex). Statistically significant (at the unadjusted 5% level) associations were seen with seven SNPs in five of the candidate genes. Two SNPs showed statistically significant association with more than one BMD site. Significant association was seen between BMD at all the three sites with the VDR SNP rs731246 (L2–L4 p = 0.038; neck of femur p = 0.001; and total hip p < 0.001). The T allele was consistently associated with lower BMD than the C allele. Significant association was also seen for the P2RX7 SNP rs3751143, where the G allele was consistently associated with lower BMD than the T allele (L2–L4 p = 0.069; neck of femur p = 0.024; and total hip p = 0.045).

Epidemiology and awareness of osteoporosis: a viewpoint from the Middle East and North Africa

“…Sassi et al [46] analyzed the association of other VDR polymorphisms (ApaI and TaqI) with BMD in postmenopausal Tunisian women and an increased risk to develop osteopenia, but not OP, was shown which strengthens the hypothesis that OP results from the interaction of genetic and environmental factors. The relationship of the 21 single nucleotide polymorphisms (SNP) in 7 selected candidate genes (LRP5, RANK, RANKL, ESR1, VDR, P2XR7, and OPG) with BMD at different body sites was evaluated in an Iranian population [47]. The overall pattern of association of these established risk SNPs were similar to those observed in other populations.…”

Association of RANKL and OPG Gene Polymorphism in Arab Women with and without Osteoporosis

“…Polymorphisms in OPG and RANKL have been associated with BMD or PMO in different genome-wide association studies derived from Europeans and East Asians [ 25 , 26 ]. The pathogenic mechanism of OPG and RANKL gene variants in osteoporosis development remains unclear since previous studies have reported contradictory findings [ 2 , 27 , 28 , 29 ]. The present study is the first to provide information on the association of RANKL and OPG gene polymorphism with osteoporosis phenotype in Saudi Arabian postmenopausal women.…”

BONE DENSITOMETRY INDICATORS IN POSTMENOPAUSAL WOMEN DEPENDING ON TNFSF11 GENE RS9594738 (C>T) POLYMORPHISM

“…Выявлено несколько мутаций гена TNFSF11, одной из которых является поли-морфизм rs9594738 (C>T). К настоящему времени выполнено ряд исследований, направленных на изучение роли данного полиморфизма в форми-ровании остеопороза и возникновение переломов [7][8][9]11]. Однако полученные в них результаты имеют определенные противоречия.…”

“…Кроме того, они не выполняли денситометрию ко-стей предплечья. Исследование женщин и муж-чин, проживающих в Иране, также позволило об-наружить ассоциацию полиморфизма rs9594738 (C>T) гена TNFSF11 с МПК поясничных позвонков, но не бедренной кости [8].…”