Susceptibility genes for osteoporotic fracture in postmenopausal Chinese women.
To identify the susceptibility genes for osteoporotic fracture in postmenopausal Chinese women, a two-stage case-control association study using joint analysis was conducted in 1046 patients with nontraumatic vertebra, hip, or distal radius fractures and 2303 healthy controls. First, 113 single-nucleotide polymorphisms (SNPs) in 16 potential osteoporosis candidate genes reported in recent genomewide association studies, meta-analyses studies, large-scale association studies, and functional studies were genotyped in a small-sample-size subgroup consisting of 541 patients with osteoporotic fractures and 554 healthy controls. Variants and haplotypes in SPTBN1, TNFRSF11B, CNR2, LRP4, and ESR1 that have been identified as being associated with osteoporotic fractures were further reanalyzed in the entire case-control group. We identified one SNP in TNFRSF11B (rs3102734), three SNPs in ESR1 (rs9397448, rs2234693, and rs1643821), two SNPs in LRP4 (rs17790156 and rs898604), and four SNPs in SPTBN1 (rs2971886, rs2941583, rs2941584, and rs12475342) were associated with all of the broadly defined osteoporotic fractures. The most significant polymorphism was rs3102734, with increased risk of osteoporotic fractures (odds ratio, 1.35; 95% confidence interval [CI], 1.17-1.55, Bonferroni p = 2.6 × 10(-4) ). Furthermore, rs3102734, rs2941584, rs12475342, rs9397448, rs2234693, and rs898604 exhibited significant allelic, genotypic, and/or haplotypic associations with vertebral fractures. SNPs rs12475342, rs9397448, and rs2234693 showed significant genotypic associations with hip fractures, whereas rs3102734, rs2073617, rs1643821, rs12475342, and rs2971886 exhibited significant genotypic and/or haplotypic associations with distal radius fractures. Accordingly, we suggest that in addition to the clinical risk factors, the variants in TNFRSF11B, SPTBN1, ESR1, and LRP4 are susceptibility genetic loci for osteoporotic fracture in postmenopausal Chinese women.
Department of Osteoporosis and Bone Diseases, Metabolic Bone Disease and Genetics Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Chun
C
Wang
Zeng
Z
Zhang
Hao
H
Zhang
Jin-Wei
JW
He
Jie-Mei
JM
Gu
Wei-Wei
WW
Hu
Yun-Qiu
YQ
Hu
Miao
M
Li
Yu-Juan
YJ
Liu
Wen-Zhen
WZ
Fu
Hua
H
Yue
Yao-Hua
YH
Ke
Zhen-Lin
ZL
Zhang
D000368:Aged; D044466:Asian People / Q000235:genetics; D015519:Bone Density / Q000235:genetics; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006620:Hip Fractures / Q000235:genetics*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000235:genetics*; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics* / Q000502:physiology; D013049:Spectrin / Q000235:genetics
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D053244:Osteoprotegerin; C452439:SPTBN1 protein, human; C506030:TNFRSF11B protein, human; D013049:Spectrin