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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 analyze the polymorphism of angiotensin-converting enzyme (ACE) gene and the gene of endothelial nitric oxide synthase (eNOS) G894T in patients with coronary heart disease (CHD) to explore the relationship between gene polymorphism and coronary heart disease Clinical significance of genetic mechanism in the pathogenesis and prognosis of coronary heart disease. Methods The polymorphisms of ACE and eNOS in 236 patients with coronary heart disease and 190 normal subjects were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Blood lipids, blood glucose, body mass index (BMI), left ventricular ejection fraction (LVEF) and blood pressure were measured simultaneously. Results The frequency of DD genotype in CHD patients was significantly higher than that in the control group [36% (36/190), P <0.01], and type Ⅱ frequency (27%, 64/236) Lower than the control group [49% (93/190), P <0.05]. The DD triglyceride (TG) [(2.2 ± 1.7) mmol / L] in coronary heart disease group was significantly higher than that of TG [(1.6 ± 0.8) mmol / L and ID [ (P <0.05)], DD (P <0.05), HDL-C (1.2 ± 0.4) mmol / L and HDL- (6.2 ± 1.7) mmo] / L and BMI [(25.7 ± 2.8) kg / m ~ 2] were significantly higher than those of ID type [glucose: (5,6 ± 1.3) mmol / L, (P <0.05). The LVEF of DD type (56% ± 14%) was significantly lower than that of type Ⅱ LVEF (62% ± 15%) and ID type LVEF (61% ± 14% P <0.05. Systolic blood pressure, diastolic blood pressure, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), diabetes and non-diabetic group, acute coronary syndrome group and non-acute coronary syndrome group, There was no significant difference between ACE and eNOS genotypes in multi-vessel disease group. The frequency of GT genotype of eNOS gene in coronary heart disease group was significantly higher than that in control group [28% (67/236) [17% (32/190), P <0.01]. There was no significant difference in the frequency of GG between the two groups. TG, HDL-C, blood glucose, BMI and LVEF were not significantly different between different genotypes of eNOS (all P> 0.05). The risk of CHD with DD type was 1.74 times that of type II carrier (P <0.01). The probability of carrying coronary artery disease with GT type was 1.73 times that of GG type (P <0.05). The interaction between the two genes in patients with coronary heart disease showed that patients carrying type II and GG at the same time had a 37.9% probability of having coronary heart disease, while those with type DD and type GT carrying coronary heart disease were 77.8%. Conclusions ACE gene polymorphism and eNOS gene polymorphism are significantly associated with coronary heart disease and some risk factors. When carrying both genotypes DD and GT, the risk of coronary heart disease is significantly increased, with significant genetic tendency.