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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TT75%(41/55),TM18%(10/55),MM7%(4/55);健康对照组TT83%(50/60),TM15%(9/60),MM2%(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(χ2=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(χ2=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。
BACKGROUND: Most scholars believe that 174M polymorphism of angiotensinogen T gene is one of the genetic predisposition factors of coronary heart disease, hypertension and myocardial infarction. Objective: To investigate the relationship between angiotensinogen gene T174M mutation and myocardial infarction. Design: Case-Controlled Validation Experiment. Unit: Department of Cell Biology and Department of Biochemistry and Molecular Biology, Department of Biological Sciences, North China Coal Medical College, Department of Cardiology, North China Coal Medical College Affiliated Hospital. PARTICIPANTS: A total of 55 patients with cardiovascular inpatient and inpatient myocardial infarction from Tangshan Workers Hospital and North China Coal Medical College from September 2002 to September 2003 were selected, including 29 males and 26 females, aged 60 ± 8 years. Over the same period, 60 outpatients (32 healthy controls), 32 males and 28 females, aged 60 ± 10 years, were enrolled in the study. No coronary heart disease performance, no family history of myocardial infarction or cerebral infarction history. Participant informed consent. Intervention: Amplification of the gene exon 2 of angiotensinogen gene by polymerase chain reaction, including the sequence encoding the amino acid residue at position 174, Nco I restriction endonuclease digestion, restriction fragment length polymorphism analysis of blood vessels The genotypes of ET were detected, and the risk factors related to the incidence of CHD were also detected, such as blood pressure, body weight, blood lipid, fasting blood glucose and other two groups of people. MAIN OUTCOME MEASURES: ① Genotype distribution, genotype frequency and allele frequency in both groups. ② the incidence of risk factors in both groups. Results: All 115 subjects completed the design and entered the result analysis. ① The frequencies of angiotensinogen genotypes were TT75% (41/55), TM18% (10/55) and MM7% (4/55) in the myocardial infarction group, TT83% (50/60), TM15% 9/60), MM2% (1/60). M174 and T174 allele frequencies were 16% (18/110), 84% (92/110), and 9% (11/120), 91% (109/120), respectively, in myocardial infarction and control groups Group M174 allele frequency was significantly higher than the healthy control group (χ2 = 5.79, P <0.05). According to gender grouping, the frequencies of M and T allele in the male and female myocardial infarction group were basically the same. The type of angiotensinogen 174MM in patients with myocardial infarction was significantly higher than that in healthy controls (χ2 = 7.55, P <0.025). ② Risk factors: The proportion of smoking history in myocardial infarction group was significantly higher than that in healthy control group (P = 0.006) .After correcting the main risk factors of coronary heart disease, angiotensinogen gene 174MM still significantly increased the incidence of myocardial infarction Risk (odds ratio 3.66, P = 0.018). Conclusion: The genotype of angiotensinogen is related to the occurrence of myocardial infarction. The M allele is one of the genetic predisposing factors of myocardial infarction. The T allele has a protective effect on the occurrence of myocardial infarction. The occurrence of myocardial infarction has no correlation with sex, but angiotensinogen gene 174TM is one of the important risk factors of myocardial infarction.