广西壮族男性膜型基质金属蛋白酶1基因多态性与骨质疏松症的相关性  

Association of MMP14 gene polymorphisms and osteoporosis in Zhuang men from Baise region of Guangxi

作　　者：周庆辉[1] 黄秀峰[1] 王金花[1] 林朝文[1] 杨园园[1] 黄昌盛[1] 吴联滔[1] 吴玉梅[1] 

机构地区：[1]右江民族医学院人体解剖学教研室,右江民族医学院人类学研究所,广西壮族自治区百色市533000

出　　处：《中华医学遗传学杂志》2012年第3期309-313,共5页Chinese Journal of Medical Genetics

基　　金：基金项目：国家自然科学基金（30860117）,广西科技计划项目（桂科攻0898004）

摘　　要：目的探索膜型基质金属蛋白酶1（membrane-type 1 matrixmetalloproteinase，MT1-MMP，MMP14）基因的多态性与广西百色地区壮族男性骨质疏松症的相关性。方法用超声骨密度仪测量百色地区301名壮族男性左跟骨超声振幅衰减（broadbandultrasonicattenuation，BUA），并根据中国入骨质疏松症建议诊断标准分为正常对照、骨量减少以及骨质疏松组。应用MultiplexSNaPshotSNP分型技术确定MMPl4基因5个单核苷酸多态性（singlenucleotidepolymorphism，SNP）位点（rs1003349、rs3751488、rs2269213、rs2236303和rs743257）的基因型。结果全部位点的多态性分布均符合Hardy-Weinberg平衡（P〉0．05）。多元线性逐步回归分析提示，上述多态性与BUA变异无相关性（P〉0．05）。rs2236303位点CC基因型（VS．TT，OR=10．604，95％CI：1．899～59．228，P=0．007）、CT基因型（VS．TT，OR=5．602，95％CI：1．351～23．24，P=0．018）以及rs1003349的GT基因型（VS．GG，OR=4．884，95％CI：1．087～21．949，P=0．039）在骨质疏松组的频率显著偏高。连锁不平衡分析显示，rs1003349和rs2236303位点存在一般连锁（D’=0．839，r2=0．458，P〈0．01），两个位点的单倍型pT在骨量正常组与骨质疏松组中的频率差异有统计学意义（P〈0．05），单倍型为GT的个体发生骨质疏松症的风险显著高于C-C或T—C的个体（P〈0．05）。结论MMP14基因的rs1003349和rs2236303多态性位点可能与广西壮族男性骨质疏松症的易感性相关，rs1003349和rs2236303位点的单倍型G-C和T-C可能增加骨质疏松症的发病风险。Objective To assess the association between membrane-type 1 matrix metalloproteinase gene （MT1-MMP, MMP14）polymorphisms and osteoporosis in Zhuang men from Baise region of Guangxi. Methods Genotypesof 5 loci （rs1003349, rs3751488, rs2269213, rs2236303, rs1042704 andrs743257） of MMP14 gene in 301 Zhuang men were determined with single base extension methods, and bone mineral density （BMD） at left calcaneus was evaluated with quantitative ultrasound with measured values of broadband ultrasonic attenuation （BUA）. The subjects were divided according to BMD into osteoporosis group, osteopenia group and normal bone density group. Results All selected loci were in Hardy-Weinberg equilibrium （P^0.05）. By multiple linear stepwise regression analysis, polymorphisms of the five loci were not associated with BUA. But a significant higher risk of osteoporosis was found in individuals with MMP14 rs1003349 GT genotype （vs. GG genotype; P^0. 05） and rs2236303 CC and CT genotypes （vs. TT genotype; P^0.05）. Genetic linkage between rs1003349 and rs2236303 was also discovered （Dr =0. 839, rz =0. 458, P^0.01）. Compared with the normal bone density group, the frequency of a G-T haplotype of rs1003349 and rs2236303 was significantly lower in the osteoporosis group （P^0. 05）. And the risk of osteoporosis for individuals with G-C and T-C haplotypes was 2. 556 （95% CI： 1. 029-6. 349, P=0. 038） and 5. 111 （95% CI： 1. 341-19. 485, P=0. 011） compared with G-T haplotype. Conclusion Polymorphisms of rs1003349 and rs2236303 loci of MMP14 gene are associated with the susceptibility of osteoporosis in Zhuang men in Guangxi. G-C and T-C haplotypes for loci rs1003349 and rs2236303 may increase the disease risk.

关 键 词：膜型基质金属蛋白酶1 单核苷酸多态性 骨密度 骨质疏松症 壮族 

分 类 号：R580[医药卫生—内分泌]