Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

Abstract

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 smallsample-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 ¼ 2.6 Â 10 À4 ). 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. ß

BMP7 gene polymorphisms are not associated with bone mineral density or osteoporotic fractures in postmenopausal Chinese women

“…With the development of genetic testing technology, many candidate genes associated with BMD and osteoporosis or osteoporotic fractures have been identified [14,[23][24][25] , thus promoting the exploration of the underlying genetic mechanisms and therapeutic targets for osteoporosis, osteoporotic fractures and other diseases affecting bone metabolism. To the best of our knowledge, this is the first large-scale case-control study to identify the association between BMP7 gene polymorphisms and BMD and osteoporotic fracture in postmenopausal Chinese women, even in an Asian female population.…”

“…All participants underwent a physical examination and routine laboratory measurements. The study population consisted of 1278 postmenopausal women with osteoporotic fractures (OF group) and 2642 healthy women without fractures (control group) [14] . The subjects in the OF group had at least one osteoporotic fracture in the vertebra, hip or distal radius.…”

“…The subjects in the OF group had at least one osteoporotic fracture in the vertebra, hip or distal radius. The criteria for exclusion from this study were described in our previous study [14] . Briefly, we excluded subjects who were receiving treatment or had medical complications known to affect bone metabolism.…”

“…The identification of osteoporotic fractures was performed as described previously [14] . Nontraumatic fractures were defined as resulting from a fall from standing height or less or as manifesting without any trauma [18] .…”

Protein-protein interaction network and significant gene analysis of osteoporosis

“…In western countries, 30% of women and 20% of men have had osteoporotic fractures, resulting in medical expenses in the United Kingdom the United States of up to 1.4 and 1.5 billion dollars, respectively (Cummings and Melton, 2002). As a developing country in Asia, China has a large population base, which is aging at a rapid rate, making osteoporosis and fractures an increasingly severe public health problem (Kung et al, 2007;Wang et al, 2012). Symptoms of osteoporosis patients are often missed, which can only be diagnosed once the bone is fractured.…”