Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men |
| |
Authors: | Yi-Hsiang Hsu Tianhua Niu Henry A. Terwedow Xin Xu Yan Feng Zhiping Li Joseph D. Brain Cliff J. Rosen Nan Laird Xiping Xu |
| |
Affiliation: | (1) Program for Population Genetics, Harvard School of Public Health, 665 Huntington Avenue, FXB-101, Boston, MA, USA;(2) Division of Preventive Medicine, Department of Medicine, Brigham and Women Hospital, Harvard Medical School, Boston, MA, USA;(3) Institute of Medicine, Anhui Medical University, Anhui, China;(4) Maine Center for Osteoporosis Research and Education, St. Joseph Hospital, Bangor, ME, USA;(5) Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA |
| |
Abstract: | In order to assess the contribution of polymorphisms in the RANKL (TNFSF11), RANK (TNFRSF11A) and OPG (TNFRSF11B) genes to variations in bone mineral density (BMD), a population-based cohort with 1,120 extreme low hip BMD cases or extreme high hip BMD controls was genotyped on five SNPs. We further explored the associations between these genetic variations and forearm BMDs by genotyping 266 offspring and 309 available parents from 160 nuclear families. A family-based association test was used. Significantly positive associations were found for A163G polymorphisms in the promoter regions of the OPG gene, a missense substitution in exon 7 (Ala192Val) of the RANK gene and rs9594782 SNP in the 5′ UTR of the RANKL gene with BMD in men only. Men with TC/CC genotypes of the rs9594782 SNP had a 2.1 times higher risk of extremely low hip BMD (P=0.004), and lower whole body BMD (P<0.001). Subjects with the TC genotype of the Ala192Val polymorphism had a 40% reduced risk of having extremely low hip BMD (P<0.01), and higher whole body BMD (P<0.01). Subjects with the GG genotype of the A163G polymorphism had a 70% reduced risk of having extremely low hip BMD (P<0.05), and higher whole body BMD (P<0.01). Significant gene–gene interactions were also observed among the OPG, RANK and RANKL genes. Our findings suggest that genetic variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are strongly associated with BMD at different skeletal sites in adult men, but not in women. Electronic Supplementary Material Supplementary material is available for this article at |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|