Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Georgetown University, Washington, DC, USA.
Acta Pharmacol Sin. 2019 Sep;40(9):1212-1218. doi: 10.1038/s41401-019-0219-7. Epub 2019 Mar 5.
Plastin 3 (PLS3) has been identified as a candidate gene for bone fragility in the Rotterdam study (RS) population. So far, however, whether PLS3 polymorphisms are genetic risk factors for osteoporosis in Asian population remains unclear. In order to investigate the association between genetic variants in PLS3 and the risk of fragility fracture and/or bone mineral density (BMD) in postmenopausal Chinese women, we conducted a case-control association study. A total of 1083 postmenopausal patients with osteoporotic fractures and 2578 unrelated non-fracture controls in Shanghai were enrolled. Seven SNPs, including six tagSNPs in PLS3 and one identified genetic risk factor (rs140121121) for osteoporosis in the RS population, were genotyped in all the participants. BMD at lumbar spine and hip sites were measured in 2578 controls. Association between SNPs and the risk of osteoporotic fractures and/or BMD were analyzed. The GC genotype of rs757124 and AC genotype of rs10521693 were associated with lumbar vertebral fracture (P = 0.020 and 0.046, respectively). The association between tagSNPs and BMD were analyzed only in 2546 controls to avoid biased conclusion. rs757124 was significantly associated with BMD at lumbar spine and hip sites. GG genotype had the highest BMD at lumbar spine (L1-4), while CC genotype had the highest BMD at hip sites. Our results suggest that polymorphisms in PLS3 are genetic loci for osteoporosis in postmenopausal Chinese women.
PLASTIN 3（PLS3）已被确定为鹿特丹研究（RS）人群中骨脆弱的候选基因。然而，到目前为止，PLS3 多态性是否是亚洲人群骨质疏松症的遗传危险因素尚不清楚。为了研究 PLS3 基因变异与绝经后中国妇女脆性骨折和/或骨密度（BMD）风险之间的关系，我们进行了病例对照关联研究。共纳入上海 1083 例骨质疏松性骨折的绝经后患者和 2578 例无骨折的无关对照。在所有参与者中检测了 PLS3 中的 7 个 SNP，包括 6 个标签 SNP 和 RS 人群中确定的骨质疏松症遗传危险因素（rs140121121）。在 2578 例对照中测量了腰椎和髋部的 BMD。分析了 SNP 与骨质疏松性骨折和/或 BMD 的风险之间的关系。rs757124 的 GC 基因型和 rs10521693 的 AC 基因型与腰椎骨折相关（P=0.020 和 0.046）。仅在 2546 例对照中分析了标签 SNP 与 BMD 的关系，以避免得出有偏差的结论。rs757124 与腰椎和髋部 BMD 显著相关。GG 基因型在腰椎（L1-4）处具有最高的 BMD，而 CC 基因型在髋部具有最高的 BMD。我们的研究结果表明，PLS3 中的多态性是绝经后中国妇女骨质疏松症的遗传位点。
