Literature DB >> 25138264

Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women.

P Tu1, P Duan, R-S Zhang, D-B Xu, Y Wang, H-P Wu, Y-H Liu, L Si.   

Abstract

UNLABELLED: Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women.
INTRODUCTION: The aim of this study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in a cohort of Chinese post-menopausal women.
METHODS: A cross-sectional study was conducted in 881 post-menopausal women aged 50-89 years. All participants underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were genotyped. We tested whether a single SNP or a haplotype was associated with BMD variations.
RESULTS: Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and one in the TNFRSF11A gene (rs7239261) were found to be significantly associated with FN BMD (p = 0.014, 0.013, and 0.047, respectively). Haplotype TGACGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic risk factor toward a lower FN BMD (beta = -0.1473; p = 0.01126). In contrary, haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was genetic protective factor for LS BMD (beta = 0.3923; p = 0.04917).
CONCLUSIONS: Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health.

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Year:  2014        PMID: 25138264     DOI: 10.1007/s00198-014-2854-7

Source DB:  PubMed          Journal:  Osteoporos Int        ISSN: 0937-941X            Impact factor:   4.507


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