CAJ | 학술논문

目的探索膜型基质金属蛋白酶1(membrane-type l matrix metalloproteinase,MTl-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(broadband ultrasonic attenuation,BUA),并根据中国人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Multiplex SNaPshot SNP分型技术确定MMP14基因5个单核苷酸多态性(single nucleotide polymorphism,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G-T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G-T的个体发生骨质疏松症的风险显著高于G-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.
목적 탐색막형기질금속단백매1(membrane-type l matrix metalloproteinase,MTl-MMP,MMP14)기인적다태성여엄서백색지구장족남성골질소송증적상관성.방법 용초성골밀도의측량백색지구301명장족남성좌근골초성진폭쇠감(broadband ultrasonic attenuation,BUA),병근거중국인골질소송증건의진단표준분위정상대조、골량감소이급골질소송조.응용Multiplex SNaPshot SNP분형기술학정MMP14기인5개단핵감산다태성(single nucleotide polymorphism,SNP)위점(rs1003349、rs3751488、rs2269213、rs2236303화rs743257)적기인형.결과 전부위점적다태성분포균부합Hardy-Weinberg평형(P＞0.05).다원선성축보회귀분석제시,상술다태성여BUA변이무상관성(P＞0.05).rs2236303위점CC기인형(vs.TT,OR=10.604,95％CI:1.899～59.228,P=0.007)、CT기인형(vs.TT,OR=5.602,95％CI:1.351～23.24,P=0.018)이급rs1003349적GT기인형(vs.GG,OR=4.884,95 ％CI;1.087～21.949,P=0.039)재골질소송조적빈솔현저편고.련쇄불평형분석현시,rs1003349화rs2236303위점존재일반련쇄(D′=0.839,r2 =0.458,P＜0.01),량개위점적단배형G-T재골량정상조여골질소송조중적빈솔차이유통계학의의(P＜0.05),단배형위G-T적개체발생골질소송증적풍험현저고우G-C혹T-C적개체(P＜0.05).결론 MMP14기인적rs1003349화rs2236303다태성위점가능여엄서장족남성골질소송증적역감성상관,rs1003349화rs2236303위점적단배형G-C화T-C가능증가골질소송증적발병풍험.
[Objective]To assess the association between membrane-type 1 matrix metalloproteinsse gene (MT1-MMP,MMP14)polymorphisms and osteoporosis in Zhuang men from Baise region of Guangxi.[Methods] Genotypes of 5 loci (rs1003349,rs3751488,rs2269213,rs2236303,rs1042704 and rs743257) 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 (D′ =0.839,r2 =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％ Cl: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.