title: Analysis of recently identified osteoporosis susceptibility genes in Han Chinese women.
abstract: BACKGROUND
  In Europeans and populations of European origin, several osteoporosis susceptibility genes, including ZBTB40, RANK, RANKL, OPG, MHC, and ESR1, were recently identified. However, none of these has been fully investigated in Han Chinese populations.
  
  
  OBJECTIVE
  In this relatively large cross-sectional sample of 1012 Han Chinese women, 21 single-nucleotide polymorphisms (SNPs) within 11 candidate genes that were newly identified in Europeans were tested, and their associations with bone mineral densities (BMDs) and osteoporotic fracture were investigated.
  
  
  RESULTS
  A total of 21 SNPs were genotyped. Five SNPs in four genes [ZBTB40 (rs7524102, rs6696981), ESR1 (rs9479055), OPG (rs6469804), and RANK (rs3018362)] were found to be associated with lumbar spine BMD. Seven SNPs in five genes [ZBTB40 (rs7524102, rs6696981), OPG (rs6993813, rs6469804), RANK (rs3018362), LRP5 (rs3736228), and SOST (rs1513670)] were found to be associated with total hip BMD. SPTBN1 (rs11898505) and SOST (rs1107748) were associated with osteoporotic fracture. A significant gene-gene interaction for osteoporotic fracture involving rs1107748 in SOST and rs6469804 in OPG gene was identified from generalized multifactor dimensionality reduction analysis.
  
  
  CONCLUSIONS
  Our study provides an independent replication of the associations between several SNPs in ZBTB40, ESR1, OPG, RANK, LRP5, and SOST with lumbar spine and/or total hip BMDs in a large sample of Han Chinese women. The results of this study further support the significant associations found between osteoporotic fracture and SNPs in SPTBN1 and SOST. Our results suggest that these variants represent osteoporosis susceptibility genes in both Han Chinese and European populations.
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai, China.
authors.forename: Jian-min
authors.initials: JM
authors.lastname: Liu
authors.forename: Min-jia
authors.initials: MJ
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Zhi-bin
authors.initials: ZB
authors.lastname: Li
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Zhao
authors.forename: Li-hao
authors.initials: LH
authors.lastname: Sun
authors.forename: Bei
authors.initials: B
authors.lastname: Tao
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D044466:Asian People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010024:Osteoporosis / Q000208:ethnology / Q000235:genetics*; D053244:Osteoprotegerin / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D053244:Osteoprotegerin; C422903:SOST protein, human