Gao Li-Hong, Li Shan-Shan, Shao Chong, Fu Wen-Zhen, Liu Yu-Juan, He Jin-Wei, Zhang Zhen-Lin
Metabolic Bone Diseases and Genetic Research Unit, Division of Osteoporosis and Bone Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Acta Pharmacol Sin. 2016 Aug;37(8):1076-82. doi: 10.1038/aps.2016.28. Epub 2016 Jun 6.
A previous study shows that bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with bone mineral density (BMD) in 920 European Americans. To determine the association of BMP7 polymorphisms and BMD and osteoporotic fracture susceptibility, we performed a case-control association study in postmenopausal Chinese women with or without osteoporotic fracture.
A total of 3815 unrelated postmenopausal Chinese women (1238 with osteoporotic fracture and 2577 healthy controls) were recruited. BMDs of the lumbar spine 1-4 (L1-4) and proximal femur (including total hip and femoral neck) were measured using dual-energy X-ray absorptiometry. Eight tagging single nucleotide polymorphisms (SNPs) in BMP7 gene, including rs11086598, rs4811822, rs12481628, rs6025447, rs230205, rs17404303, rs162316 and rs6127980, were genotyped.
Among the 8 SNPs, rs6025447 and rs230205 were associated with total hip BMD (P=0.013 and 0.045, respectively). However, the associations became statistically insignificant after adjusting for age, height and weight. The TGTG haplotype of BMP7 gene was associated with total hip BMD (P=0.032), even after adjusting for age, height and weight (P=0.048); but the association was insignificant after performing the Bonferroni multiple-significance-test correction. Moreover, the 8 SNPs and 9 haplotypes of BMP7 gene were not associated with L1-4 or femoral neck BMD or osteoporotic fracture.
This large-sample case-control association study suggests that the common genetic polymorphisms of BMP7 gene are not major contributors to variations in BMD or osteoporotic fracture in postmenopausal Chinese women.
先前一项研究表明,骨形态发生蛋白7(BMP7)基因多态性与920名欧裔美国人的骨密度(BMD)相关。为了确定BMP7基因多态性与BMD及骨质疏松性骨折易感性之间的关联,我们对有或无骨质疏松性骨折的绝经后中国女性进行了一项病例对照关联研究。
共招募了3815名无亲属关系的绝经后中国女性(1238名有骨质疏松性骨折,2577名健康对照)。使用双能X线吸收法测量第1 - 4腰椎(L1 - 4)和股骨近端(包括全髋和股骨颈)的骨密度。对BMP7基因中的8个标签单核苷酸多态性(SNP)进行基因分型,包括rs11086598、rs4811822、rs12481628、rs6025447、rs230205、rs17404303、rs162316和rs6127980。
在这8个SNP中,rs6025447和rs230205与全髋骨密度相关(P分别为0.013和0.045)。然而,在调整年龄、身高和体重后,这些关联在统计学上变得不显著。BMP7基因的TGTG单倍型与全髋骨密度相关(P = 0.032),即使在调整年龄、身高和体重后(P = 0.048);但在进行Bonferroni多重显著性检验校正后,该关联不显著。此外,BMP7基因的8个SNP和9个单倍型与L1 - 4或股骨颈骨密度或骨质疏松性骨折无关。
这项大样本病例对照关联研究表明,BMP7基因的常见遗传多态性不是绝经后中国女性骨密度或骨质疏松性骨折变异的主要影响因素。