心肌梗死与血管紧张素原基因T174M多态性的关联

背景多数学者认为血管紧张素原T基因174M多态性是冠心病、高血压及心肌梗死的遗传易患因素之一.目的探讨血管紧张素原基因T174M变异与心肌梗死的关系.设计病例-对照的验证性实验.单位华北煤炭医学院生物科学系的细胞生物学教研室和生物化学与分子生物学教研室,华北煤炭医学院附属医院的心内科.对象选择2002-09/2003-09唐山市工人医院及华北煤炭医学院附属医院心血管内科门诊及住院心肌梗死患者55例,男29例,女26例,年龄(60±8)岁.同期选择门诊健康体检人群(无重复体检者)60例(健康对照组),男32例,女28例,年龄(60±10)岁.无冠心病的表现,家族史中无心肌梗死或脑梗死史.参与者知情同意.干预应用聚合酶链反应扩增血管紧张素原基因第2外显子包含编码第174位氨基酸残基的基因序列,NcoⅠ限制性内切酶切后电泳,限制性片段长度多态性分析血管紧张素原基因型,同时检测两组人群的血压、体质量、血脂、空腹血糖等与冠心病发病相关的危险因素.主要观察指标①两组基因型分布、基因型频率、等位基因频率.②两组发病的危险因素分析.结果115例观察对象均完成设计并进入结果分析.①血管紧张素原基因型频率心肌梗死组TT 75%(41/55),TM 18%(10/55),MM 7%(4/55);健康对照组TT 83%(50/60),TM 15%(9/60),MM 2%(1/60).M174与T174等位基因频率在心肌梗死组和对照组分别为16%(18/110),84%(92/110)和9%(11/120),91%(109/120),心肌梗死组M174等位基因频率显著高于健康对照组(x2=5.79,P＜0.05).按性别分组后,男性和女性心肌梗死组的M和T等位基因频率对照组基本一致.心肌梗死组患者血管紧张素原基因174MM型显著高于健康对照组(x2=7.55,P＜0.025).②危险因素比较心肌梗死组曾有吸烟史的比例显著高于健康对照组(P=0.006);经校正冠心病的主要危险因素后,血管紧张素原基因174MM仍可显著增加心肌梗死发生的危险性(比数比3.66,P=0.018).结论血管紧张素原基因型与心肌梗死的发生有关,M等位基因是心肌梗死的遗传易感因子之一,T等位基因对心肌梗死的发生有保护作用.心肌梗死的发生与性别无相关性,但血管紧张素原基因174TM是心肌梗死发病的重要危险因素之一.

Correlation between myocardial infarction and angiotensinogen T174M

BACKGROUND: A majority scholars views that polymorphism of angiotensinogen T174M gene is one of the susceptible factors of inheritance of coronary heart disease, hypertension and myocardial infarction.OBJECTIVE: To probe into the relationship between the variation of angiotensinogen T174M gene and myocardial infarction.DESIGN: Case-controlled verified experiment.SETTING: Department of Cell Biology, Biochemistry and Molecular Biology, Biological Science Faculty of North China Coal Medical College,and Department of Cardiology in Affiliated Hospital of North China Coal Medical College.PARTICIPANTS: Fifty-five cases of myocardial infarction were collected from outpatients and inpatients in Department of Cardiac Vascular Internal Medicine of Worker's Hospital Affiliated to North China Coal Medical College in Tangshan from September 2002 to September 2003, of which,29 cases were males and 26 cases females, aged (60±8) years. At the same time, 60 cases (health control) were selected from the people who received clinical physical health check (without repeated physical check), of which,32 cases were males and 28 cases females, aged (60±10) years. The cases selected had no manifestation of coronary heart disease, without history myocardial infarction or cerebral infarction in family and the participants were in the know of the research.INTERVENTIONS: Polymerase chain reaction was used to amplify the genetic sequence of No.174 DAN residue involved in No.2 exon of angiotensinogen gene. Electrophoresis was used after variated with Nco I restriction endonuclease. Analysis of restriction fragment length polymorphism was carried on angiotensinogen genotype. Simultaneously,the relevant risk factors of coronary heart disease were detected in two groups, such as blood pressure, body mass, blood lipid, fasting blood glucose, etc.MAIN OUTCOME MEASURES: ① Distribution of genotype, frequency of genotype and frequency of allele in two groups. ② Analysis on risk factors of two groups.RESULTS: Totally 115 cases of objects all accomplished the design and entered result analysis. ① Frequency of angiotensinogen genotype: in myocardial infarction group, TT 75％ (41/55), TM 18％ (10/55), MM 7％ (4/55) and in control group, TT 83％ (50/60), TM 15％ (9/60), MM 2％ (1/60). Frequency of allele of M174 and T174 were 16％ (18/110), 84％ (92/110) and 9％ (11/120), 91％ (109/120) in myocardial infarction group and control group respectively. Frequency of allele of M174 in myocardial infarction group was significantly higher than that of control group (x2=5.79,P ＜ 0.05). By the division of sex, the frequency M and T alleles of both male and female in experiment group was basically identical to control group. Angiotensinogen 174MM genotype in myocardial infarction group was significantly higher than control group (x2= 7.55, P ＜ 0.025). ② Comparison of risk factors: The percentage of smoking history in myocardial infarction group was significantly higher than control group (P = 0.006). After correction of essential risk factors of coronary heart disease, angiotensinogen 174MM gene still increased significantly the risk of myocardial infarction (Odds ratio was 3.66, P= 0.018).CONCLUSION: Angiotensinogen genotype is related to the occurrence of myocardial infarction. M allele is one of the susceptible factors of inheritance of myocardial infarction and T allele prevents from myocardial infarction. The attack of myocardial infarction is not relevant to sex, but angiotensinogen 174TM gene is one of the essential risk factors of myocardial infarction.