Evaluation of genetical factor in the Japanese is chemic heart disease

日本人化学性心脏病遗传因素评价

基本信息

批准号：
09670743
负责人：
NAKAI Kenji
金额：
$ 1.92万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

Coronary artery disease including acute myocardial infarction is a major cause for cardiac sudden death. The pathogenesis and genetical risk factor of coronary artery disease and acute myocardial infarction have not been fuilly elucidated. The clinical research regarding genetical factors in the Japanese were worthy of note in the world, because the frequencies of several gene polymorphism were different with those in Caucasian. The purpose of this study is to evaluate the significance of genetical factors such as apolipoprotein E (apo E), angiotensin II type 1 receptor, ecNOS, and methylenetetrahydrofolate reductase (MTHFR) in the occurrence of myocardial infarction.Results: 1) The frequency of polymorphism of apo E ε4 allele and ATR1 All66C mutation [AC+CC] in the Japanese healthy population was lesser than those in Caucasian healthy population. 2) The frequency of apo E ε 4 allele and ATR1 A1166C mutation [AC+CC], esNOS 4a/a with tandem repeat, and MTHFR alanine/valine (A/V) caused by C677T mutation in the myocardial infarction were greater than those in Japanese healthy population (apo E; Nakai et al, Coronary Artery Dis, 1999). 3) Thee levels of concentration of homocysteine in MTHFR gene VV type was higher than that in other AV and AA genotype (11.6 ± 5.6 μmol/L in VV type, 8.9 ± 4.1 μmol/L in AV type and 8.6 ± 3.3 μmol/L in AA type) (Nakai K et al: Coronary Artery Dis, 1999). 4) The frequency of ATRI A1166C mutation [AC+CC] in the myocardial infarction was higher than that in healthy population (Fusazaki et al; Eur heart J, 1999).In conclusion, apo E e4 allele, A1166C mutation [AC+CC], MTHFR geneVV type were predisposition for myocardial infarction. In future, these genetical analysis enable to indicate for primary or secondary prevention for myocardial infarction or coronary artery disease.

包括急性心肌梗死在内的冠状动脉疾病是心源性猝死的主要原因，日本人的冠状动脉疾病和急性心肌梗死的发病机制和遗传危险因素尚未完全阐明，值得关注。世界各地，因为一些基因多态性的频率与白种人不同。本研究的目的是评估载脂蛋白E（apo E）等遗传因素的重要性。血管紧张素II 1型受体、ecNOS、亚甲基四氢叶酸还原酶（MTHFR）在心肌梗死发生中的作用。结果：1）日本健康人群中apo E ε4等位基因多态性和ATR1 All66C突变[AC+CC]的频率较低2) apo E ε 4 等位基因和 ATR1 的频率。心肌梗塞中A1166C突变[AC+CC]、具有串联重复的esNOS 4a/a以及C677T突变引起的MTHFR丙氨酸/缬氨酸(A/V)均大于日本健康人群(apo E；Nakai等， Coronary Artery Dis, 1999) 3) MTHFR 基因 VV 型的同型半胱氨酸浓度水平高于其他基因型。 AV 和 AA 基因型（VV 型为 11.6 ± 5.6 μmol/L，AV 型为 8.9 ± 4.1 μmol/L，AA 型为 8.6 ± 3.3 μmol/L）（Nakai K 等：Coronary Artery Dis，1999）。 ATRI A1166C突变[AC+CC]在心肌梗死人群中的频率高于健康人群(Fusazaki等人；Eur heart J，1999)。总之，apo E e4等位基因、A1166C突变[AC+CC]、MTHFR基因VV型是心肌梗塞的易感性。将来，这些遗传分析能够指示原发性或继发性心肌梗死。预防心肌梗塞或冠状动脉疾病。