title: Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Nanchang Key Laboratory of Diabetes, Nanchang, Jiangxi Province, 330009, China, tuping8877@126.com.
authors.forename: P
authors.initials: P
authors.lastname: Tu
authors.forename: P
authors.initials: P
authors.lastname: Duan
authors.forename: R-S
authors.initials: RS
authors.lastname: Zhang
authors.forename: D-B
authors.initials: DB
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H-P
authors.initials: HP
authors.lastname: Wu
authors.forename: Y-H
authors.initials: YH
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Si
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000503:physiopathology; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics / Q000502:physiology; D053245:RANK Ligand / Q000235:genetics*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human