A Candidate Gene Association Study of Bone Mineral Density in an Iranian Population.
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 genesLRP5, RANK, RANKL, OPG, P2RX7, VDR, andESR1. 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 theVDRSNP rs731246 (L2-L4p= 0.038; neck of femurp= 0.001; and total hipp< 0.001). The T allele was consistently associated with lower BMD than the C allele. Significant association was also seen for theP2RX7SNP rs3751143, where the G allele was consistently associated with lower BMD than the T allele (L2-L4p= 0.069; neck of femurp= 0.024; and total hipp= 0.045).
Department of Medical Genetics, Shiraz University of Medical Sciences , Shiraz , Iran.
Seyed Alireza
SA
Dastgheib
Academic Unit of Bone Biology, Department of Oncology and Metabolism, The Mellanby Centre for Bone Research, The University of Sheffield , Sheffield , UK.
Alison
A
Gartland
Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran; Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Seyed Mohammad Bagher
SM
Tabei
Endocrine and Metabolic Research Center, Namazi Hospital, Shiraz University of Medical Sciences , Shiraz , Iran.
Gholamhossein Ranjbar
GR
Omrani
Design Trials and Statistics, School of Health and Related Research (ScHARR), The University of Sheffield , Sheffield , UK.
Marion Dawn
MD
Teare
BMD; Iranian population; P2RX7; VDR; candidate gene association; genetic epidemiology