MTRR基因A66G多态性及血浆同型半胱氨酸水平与心肌梗死的关系
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摘要
背景与目的冠心病是当今国内外的多发病,尤其是经济发达欧美国家,是严重威胁人类健康的主要疾病之一。随着改革开放和人民生活水平的提高,我国的冠心病的患病率和死亡率呈上升的趋势。研究冠心病的发病机制是当今医学研究的重要课题之一。冠心病的传统危险因素包括:性别,年龄,高血压,糖尿病,高胆固醇血症,吸烟和冠心病家族史等,但临床上部分患者不具备上述的危险因素,因此,寻找并研究其他冠心病的危险因素,并采取切实有效的措施降低这些危险因素,以延缓冠心病的发生和减轻冠心病的临床症状,是冠心病防治中一项长期任务。近年的基础和临床研究表明,高同型半胱氨酸也是冠心病的独立危险因素之一。大量流行病学调查证实,高同型半胱氨酸与冠心病的发病明显相关。本研究为了探讨MTRR多态性及血浆同型半胱氨酸(Hcy)水平与心肌梗死的关系。方法运用聚合酶链反应-限制性片段长度多态性技术检测180例心肌梗死患者及180例冠状动脉正常的人MTRR基因多态性,用高效液相色谱仪和荧光检测仪测定血浆总Hcy水平。
结果MTRR有3种基因型,即纯合子突变型(GG),杂合子突变型(AG)及正常野生型(AA)。心肌梗死组GG型频率为35.4%,AG型频率为53.8%,AA型频率为10.8%,G等位基因频率为62.3%,A等位基因频率为37.7%。正常组中GG型频率为20.1%,AG型频率为55.8%,AA型频率为24.1%,G等位基因频率为32.1%,A等位基因频率为67.9%,且心梗死组GG型频率高于正常组(P<0.01)。正常人群中GG基因型者血浆总Hcy水平明显高于(AA+AG)基因型者(P<0.01)。心肌梗死患者血浆总Hcy水平显著高于正常组(P<0.01)。多因素分析显示,MTRR基因突变型GG可能是心肌梗死发病的一个危险因素。
结论MTRR GG基因型突变可能升高个体血浆总Hcy水平;MTRR可能是心肌梗死的易感基因之一;MTRR基因突变型及高Hcy血症可能是心肌梗死发病的一个危险因素。
Background and Objective Coronary heart disease(CHD) is one of the main disease to threaten human’s health for the time being. In many countries,especially in the developed countries like America and some west European countries,its morbidity rates and mortality rates are increasing quickly. In our country,coronary artery disease has also been taking on obvious ascending trend and has become the leading cause of death in many cities and regions. It was already found that many risk factors countributed to the development of coronary artery disease, such as diabetes mellitus, hypertension,hypercholesterolemia,smoking,gender,age and etc.There are quite a number of“normal”persons with coronary artery disease,who are withlow scores of risk factors of CAD.Besides,there are still many difficulties in correcting or killing the risk factors.Recent studies have showed that hyerhomocysteinemia was also closely related with the development of coronary artery disease.There has been a wealth of epidemiological evidence that there are association between hyperhomocysteinemia and coronary artery disease.This study was designed to investigate the relationship of polymorphisms of methionine synthase reductase (MTRR) gene and plasma homcysteine(Hcy) levels with myocardial infarction.
Methods 180 myocaedial infarction patients and 180 coronary artery normal subjects were included in the study. The polymorphisms of their MTRR gene were analyzed using PCR-RFLP and their plasma total Hcy levels were measured using high-performance liquid chromatography and fluorescence detection methods. Results There were three kinds of genotype:GG(homozygous mytation), AG(heterozygous mutation) and AA(wild-type).The frequencies of the three genotypes were as follows:GG, 35.4%;AG, 53.8% and AA, 10.8% in mypcardial indarction patients. Meanwhile, GG, 20.1%;AG,55.8%;AA, 24.1% in coronary artery normal subjects, tespectively. The frequency of G alleles was significantly higher in myocardial infarction patients than in normal controls (62.3% and 32.1%,respectively) (P<0.01). Mean total plasma homoctsteine concentrations were significantly higher in myocardial infarction patients than in the normal subjects(P<0.01). Conclusion These results suggest that polymotphisms of MTRR gene and/or hyperhomocysteinemia may be an independent risk factor for myocardial infarction.
结果MTRR有3种基因型,即纯合子突变型(GG),杂合子突变型(AG)及正常野生型(AA)。心肌梗死组GG型频率为35.4%,AG型频率为53.8%,AA型频率为10.8%,G等位基因频率为62.3%,A等位基因频率为37.7%。正常组中GG型频率为20.1%,AG型频率为55.8%,AA型频率为24.1%,G等位基因频率为32.1%,A等位基因频率为67.9%,且心梗死组GG型频率高于正常组(P<0.01)。正常人群中GG基因型者血浆总Hcy水平明显高于(AA+AG)基因型者(P<0.01)。心肌梗死患者血浆总Hcy水平显著高于正常组(P<0.01)。多因素分析显示,MTRR基因突变型GG可能是心肌梗死发病的一个危险因素。
结论MTRR GG基因型突变可能升高个体血浆总Hcy水平;MTRR可能是心肌梗死的易感基因之一;MTRR基因突变型及高Hcy血症可能是心肌梗死发病的一个危险因素。
Background and Objective Coronary heart disease(CHD) is one of the main disease to threaten human’s health for the time being. In many countries,especially in the developed countries like America and some west European countries,its morbidity rates and mortality rates are increasing quickly. In our country,coronary artery disease has also been taking on obvious ascending trend and has become the leading cause of death in many cities and regions. It was already found that many risk factors countributed to the development of coronary artery disease, such as diabetes mellitus, hypertension,hypercholesterolemia,smoking,gender,age and etc.There are quite a number of“normal”persons with coronary artery disease,who are withlow scores of risk factors of CAD.Besides,there are still many difficulties in correcting or killing the risk factors.Recent studies have showed that hyerhomocysteinemia was also closely related with the development of coronary artery disease.There has been a wealth of epidemiological evidence that there are association between hyperhomocysteinemia and coronary artery disease.This study was designed to investigate the relationship of polymorphisms of methionine synthase reductase (MTRR) gene and plasma homcysteine(Hcy) levels with myocardial infarction.
Methods 180 myocaedial infarction patients and 180 coronary artery normal subjects were included in the study. The polymorphisms of their MTRR gene were analyzed using PCR-RFLP and their plasma total Hcy levels were measured using high-performance liquid chromatography and fluorescence detection methods. Results There were three kinds of genotype:GG(homozygous mytation), AG(heterozygous mutation) and AA(wild-type).The frequencies of the three genotypes were as follows:GG, 35.4%;AG, 53.8% and AA, 10.8% in mypcardial indarction patients. Meanwhile, GG, 20.1%;AG,55.8%;AA, 24.1% in coronary artery normal subjects, tespectively. The frequency of G alleles was significantly higher in myocardial infarction patients than in normal controls (62.3% and 32.1%,respectively) (P<0.01). Mean total plasma homoctsteine concentrations were significantly higher in myocardial infarction patients than in the normal subjects(P<0.01). Conclusion These results suggest that polymotphisms of MTRR gene and/or hyperhomocysteinemia may be an independent risk factor for myocardial infarction.
引文
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