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冠心病与血管紧张素转换酶和内皮型一氧化氮合酶基因多态性及交互作用的临床研究 被引量:8

Association between angiotensin-converting enzyme and endothelial nitric oxide synthase gene polymorphism and risk of coronary artery disease
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摘要 目的联合对冠心病患者血管紧张素转换酶(ACE)基因多态性和内皮型一氧化氮合酶(eNOS)基因 G894T 多态性进行分析,探讨基因多态性与冠心病的关系和交互作用及遗传学机制在冠心病发病及预后中的临床意义。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测236例冠心病患者及190例正常人 ACE 和 eNOS 两种基因多态性。同时测定血脂、血糖、体重指数(BMI)、左室射血分数(LVEF)和血压。结果冠心病组 ACE 基因 DD 型频率[36%(86/236)]显著高于对照组[19%(36/190),P<0.01],Ⅱ型频率[27%(64/236)]显著低于对照组[49%(93/190),P<0.05]。冠心病组 DD 型甘油三酯(TG)[(2.2±1.7)mmol/L]显著高于Ⅱ型 TG[(1.6±0.8)mmol/L 和 ID 型 TG[(1.7±0.9)mmol/L,均 P<0.05],DD 型高密度脂蛋白胆固醇[HDL-C(1.2±0.4)mmol/L]显著低于Ⅱ型 HDL-C[(1.3±0.3)mmol/L,P<0.05],DD 型血糖[(6.2±1.7)mmo]/L]和BMI[(25.7±2.8)kg/m^2]显著高于 ID 型[血糖:(5,6±1.3)mmol/L,BMI:(24.8±3.1)kg/m^2,P<0.05],DD 型 LVEF(56%±14%)显著低于Ⅱ型 LVEF(62%±15%)和 ID 型 LVEF(61%±14%),均 P<0.05。收缩压、舒张压、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、糖尿病组与非糖尿病组、急性冠状动脉综合征组与非急性冠状动脉综合征组、单支病变组与多支病变组在ACE 和 eNOS 基因不同基因型之间差异均无统计学意义。冠心病组 eNOS 基因 GT 型频率[28%(67/236)]显著高于对照组[17%(32/190),P<0.01],GG 型频率与对照组比较,差异无统计学意义。TG、HDL-C、血糖、BMI 和 LVEF 在 eNOS 基因不同基因型之间差异均无统计学意义(均 P>0.05)。携带 DD 型患冠心病的概率是携带Ⅱ型的1.74倍(P<0.01),携带 GT 型患冠心病的概率是携带 GG 型的1.73倍(P<0.05)。两种基因对患冠心病的交互作用显示为如同时携带Ⅱ型和 GG 型,患冠心病的概率是37.9%,而同时携带 DD 型和 GT 型患冠心病的概率是77.8%。结论 ACE 基因多态性和eNOS 基因多态性与冠心病及某些危险因素显著相关,同时携带 DD 型和 GT 型两种易患基因型时,患冠心病的概率明显增加,具有显著的遗传倾向。 Objective To observe the association between angiotensin-converting enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism and risk of coronary artery disease (CAD) in Han Chinese. Methods The polymorphism in the ACE and eNOS gene were detected by using polymerase chain reaction-restriction fragment length polymorphism analysis, blood pressure(BP) ,blood lipids, blood glucose(BS), body mass index (BMI) and left ventricle eject fraction (LVEF) were determined 236 patients with CAD and 190 healthy individuals. Results The frequencies of DD genotype of ACE were higher and the Ⅱ genotype were lower in CAD patients than in controls (P 〈 0. 05). CAD patients with DD genotypes were related with higher serum TG, lower HDL-C, higher BS levels, higher BWI and lower LVEF compared to CAD patients with Ⅱ and ID genotypes of ACE ( all P 〈 0. 05), while SBP, DBP, TC and LDL-C levels were similar among CAD patients and controls with different genotypes of ACE ( P 〉 0. 05). The genotype distributions of ACE and eNOS were also similar among CAD patients with or without diabetes mellitus/ACS, with single or multiple vessel diseases ( P 〉 0.05 ). The frequency of GT genotype of eNOS was higher in CAD patients than in controls ( P 〈 0. 01 ) while the frequency of GG genotype in CAD patients and controls was similar(P 〉 0. 05) and eNOS genotypes were not related to TC, TG, HDL-C,LDL-C, BS, BMI,SBP, DBP and LVEF levels among CAD patients and controls ( P 〉 0. 05 ). The risk of suffering from CAD in population with ACE DD genotype is 1.74 times higher than that with Ⅱ genotype(P 〈 0. 01 )and 1.73 times higher in population with eNOS GT genotype than that with GT genotype(P 〈0. 05). The risk of suffering from CAD is 37. 9% with Ⅱ and GG genotypes and 77. 8% with DD and GT genotypes. Conclusion The ACE and eNOS genotype polymorphisms were associated with risk of CAD and persons with DD and GT genotypes take higher risk of suffering from CAD.
出处 《中华心血管病杂志》 CAS CSCD 北大核心 2007年第11期1024-1028,共5页 Chinese Journal of Cardiology
基金 山东省科技发展计划重点项目(2004GG2202040)
关键词 冠状动脉疾病 一氧化氮合酶 肽基二肽酶A 多态性 单核苷酸 Coronary disease Nitric oxide synthase Peptidyl-dipeptidase A Polymorphism, single nucleotide
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