基质金属蛋白酶9基因多态性及与高血压交互作用和新疆汉族人群心肌梗死的相关性

Interactions Between Matrix Metalloproteinase-9 Polymorphism and Hypertension in Relation to Myocardial Infarction in a Chinese Population

目的探讨基质金属蛋白酶9(MMP-9)基因启动子区-1562C>T多态性及与高血压的交互作用和新疆地区汉族人群心肌梗死的相关性。方法选择2006-02-2009-12在新疆医科大学第一附属医院心脏中心住院并行冠状动脉造影检查确诊的汉族心肌梗死患者362例(病例组);对照组419例,为同期入院行冠状动脉造影检查结果阴性排除冠心病者。采用聚合酶链反应-限制性片段长度多态性方法对所有纳入对象MMP-9基因启动子区-1562C>T多态性进行分析,比较两组间基因型和等位基因频率分布的差异。结合造影情况,探讨MMP-9基因多态性与心肌梗死发病及冠脉狭窄程度的关系,并分析其和高血压的交互作用。结果病例组和对照组CT+TT基因型频率分别为26.5%和17.0%,两组比较差异有统计学意义(χ2=10.59,P=0.001),病例组T等位基因频率也高于对照组,差异有统计学意义(14.9%比8.9%,χ2=13.37,P<0.01)。携带CT/TT基因型合并高血压个体发生心肌梗死的风险明显高于携带CC基因型无高血压者(OR=5.87,95%CI3.08～11.18)。多因素logistic回归分析显示,-1562T等位基因、高血压及T等位基因与高血压的交互作用均是心肌梗死发生的独立风险因素,OR值分别为1.596、2.991和5.799。不同冠脉病变支数亚组各基因型分布比较差异无统计学意义(χ2=1.34,P=0.51)。结论 MMP-9基因-1562C>T多态性可能与新疆地区汉族人群心肌梗死的发生相关;-1562T等位基因可能是心肌梗死遗传易感性的基因标记之一;-1562变异基因型与高血压在心肌梗死的发生中可能存在协同作用;-1562C>T多态性与心肌梗死冠脉狭窄程度无关。

Objective To investigate matrix metalloproteinase-9 （MMP-9） polymorphism （-1562CT） and its interaction between hypertension in myocardial infarction （MI） patients in a Chinese population from Xinjiang. Methods The study was a case-control study. A total of 781 subjects were recruited from February 2006 to December 2009 at our hospital. The study consisted of 362 patients with MI evidenced by coronary arteriography,419 subjects with Normal coronary arteriography,no history of heart disease and chest pain,normal electrocardiograph and blood chemistry values as control. The-1562CT polymorphism of MMP-9 gene was detected by the polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique. To investigate effects of interactions between MMP-9 polymorphism and hypertension on MI,the relationship between polymorphism in the MMP-9 gene and the severity of coronary arterial stenosis was analyzed. Results The frequency of CT and TT genotypes in patients with MI was significantly higher than in control group （χ^2=10.59,P=0.001）. The frequencies of-1562T allele were 14.9% and 8.9% in MI group and control group respectively （χ^2=13.37,P0.01）. Individual who had T allele and hypertension were at an increased risk of MI （OR=5.87,95% CI 3.08-11.18）. Logistic regression analysis also confirmed that T allele carriers （CT and TT） had a higher risk of MI （OR=1.596,95% CI 1.128-2.259）. Hypertension and it＇s interaction with MMP-9 polymorphism were independent risk factors for MI （OR=2.991 and OR=5.799,respectively）. The frequencies of CT and TT genotypes were not statistically different among MI patients with one,two,three or more significantly diseased vessels （χ^2=1.34,P=0.51）. Conclusions There results suggest that promoter （-1562CT） polymorphism of MMP-9 gene is associated with MI in this population. The T allele might be an independent risk factor for MI and there was a coordinated effect between MMP-9 variant genotypes （CT＋TT） and hypertension in the development of MI. The-1562CT polymorphism may not be useful as a predictor for the severity of coronary atherosclerosis.