对绝经后妇女骨密度和骨质疏松性骨折的多基因交互作用研究

Influences of multiple gene interactions on bone mineral density and osteoporotic fractures in postmenopausal women

目的探讨基因多态性以及基因-基因交互作用对骨密度及骨质疏松性骨折的影响。方法选取与骨密度或骨质疏松性骨折相关的23个基因的39个单核苷酸多态性（SNP）位点，在683名上海汉族绝经后女性中通过TaqMan SNP Genotyping Assay和Mass—Array Technology Platform of Sequenom等两种方法进行测定，分析这些位点与绝经后女性人群的骨密度及骨质疏松性骨折的相关关系。结果9个基因中的12个SNP位点，即rs7524102、rs6696981（ZBTB40基因），rs9479055（ESR1基因），rs6993813、rs6469804、rs11995824（OPG基因），rs3736228（LRP5基因），rs1107748（SOST基因），rs87938（CTNNB1基因），rs1366594（MEF2C基因），rs7117858（SOX6基因）以及rs10048146（FOXL1基因）与腰椎（L1-L4）或总髋部骨密度相关。位点rs11898505（SPTBN1基因）与骨质疏松性骨折相关（OR 0．522，95％CI 0．326～0．838，P=0．007）。rs1038304（ESR1）、rs1366594（MEF2C）以及rs10048146（FOXL1）三者的交互作用与骨质疏松骨折相关（P=0．0107）。结论（1）基因ZBTB40、ESR1、OPG、LRP5、SOST、CTNNB1、MEF2C、SOX6、FOXL1和SPTBN1的SNP位点与上海汉族绝经后女性的骨密度（腰椎L1—L4或总髋部）或骨质疏松性骨折相关。（2）骨质疏松性骨折的发生与ESR1、MEF2C、FOXL1三个基因的交互作用有关。

Objective To investigate the effects of the genetic polymorphisms in osteoporosis-related genes and the gene-gene interaction on bone mineral density （ BMD ） and osteoporotic fractures. Methods Thirty-nine single nucleotide polymorphism （SNP） sites in 23 genes that related to bone mineral density （ BMD ） and osteoporotic fractures were scanned in 683 Shanghai Han postmenopausal women. TaqMan SNP Genotyping Assay or Sequenom Mass ARRAY System were applied for genotyping analysis. The relation of these SNP sites with BMD and osteoporotic fractures were analyzed. Results Altogether, 12 SNPs in 9 candidate genes （ rs7524102 and rs6696981 in ZBTIM0 gene, rs9479055 in ESR1 gene, rs6993813, rs6469804, and rs11995824 in OPG gene, rs3736228 in LRP5 gene, rs1107748 in SOST gene, rs87938 in CTNNB1 gene, rs1366594 in MEF2C gene, rs7117858 in SOX6 gene, and rs10048146 in FOXL1 gene ） were associated with BMD at lumbar spine （ L1 -IA ） or total hip. In addition, rsl 1898505 in SPTBN1 gene was related to osteoporotic fractures （ OR O. 522, 95% CI O. 326-0. 838, P = 0. 007 ）. Gene-gene interaction involving rs1038304 in ESR1 gene, rs1366594 in MEF2C gene, and rs10048146 in FOXL1 gene was associated with osteoporotic fractures （ P = 0. 010 7 ）. Conclusions （ 1 ） SNPs in gene ZBTB40, ESR1, OPG, LRP5, SOST, CTNNB1, MEF2C, SOX6, FOXL1, and SPTBN1 are associated with BMD of lumbar spine or total hip, as well as osteoporotic fractures. （ 2 ） Gene-gene interaction involving rs1038304, rs1366594, and rs10048146 may contribute to the risk of osteoporotic fractures.