Yoshida Tetsuro, Yajima Kazuhiro, Hibino Takeshi, Kato Kimihiko, Matsuo Hitoshi, Segawa Tomonori, Watanabe Sachiro, Oguri Mitsutoshi, Yokoi Kiyoshi, Nozawa Yoshinori, Kimura Genjiro, Yamada Yoshiji
Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.
Int J Mol Med. 2007 Oct;20(4):581-90.
Hyperlipidemia or dyslipidemia is one of the most important risk factors for coronary heart disease. The purpose of the present study was to identify gene polymorphisms for assessment of the genetic risk for myocardial infarction (MI) in individuals with low or high serum concentrations of high- density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, or triglyceride (TG), thereby contributing to the personalized prevention of MI in such individuals. The study population comprised 2682 unrelated Japanese individuals (1796 men, 886 women), including 1113 subjects (869 men, 244 women) with MI and 1569 controls (927 men, 642 women). The genotypes for 164 polymorphisms of 137 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analyses and stepwise forward selection procedures revealed that seven different polymorphisms were significantly (P<0.005) associated with MI in individuals with low or high serum concentrations of HDL- or LDL-cholesterol or of TG: the 190T --> C (Trp64Arg) polymorphism of ADRB3 in individuals with low HDL-cholesterol; the 1018C --> T (Thr145Met) polymorphism of GP1BA, the A --> G (Ile646Val) polymorphism of AKAP10, and the -55C --> T polymorphism of UCP3 in individuals with high HDL-cholesterol; the -603A --> G polymorphism of F3 and the -11377C --> G polymorphism of ADIPOQ in individuals with low LDL-cholesterol; the 1018C --> T polymorphism of GP1BA in individuals with low TG; and the 4G --> 5G polymorphism of PAI1 in individuals with high TG. No polymorphism was associated with MI in individuals with high LDL-cholesterol. These results suggest that polymorphisms associated with MI may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of MI based on genetic information.
高脂血症或血脂异常是冠心病最重要的危险因素之一。本研究的目的是鉴定基因多态性，以评估血清高密度脂蛋白（HDL）胆固醇、低密度脂蛋白（LDL）胆固醇或甘油三酯（TG）浓度低或高的个体发生心肌梗死（MI）的遗传风险，从而有助于对此类个体进行MI的个性化预防。研究人群包括2682名无亲缘关系的日本个体（1796名男性，886名女性），其中包括1113名MI患者（869名男性，244名女性）和1569名对照者（927名男性，642名女性）。通过将聚合酶链反应和序列特异性寡核苷酸探针与悬浮阵列技术相结合的方法，确定了137个候选基因的164个多态性位点的基因型。多变量逻辑回归分析和逐步向前选择程序显示，在血清HDL或LDL胆固醇或TG浓度低或高的个体中，7种不同的多态性与MI显著相关（P<0.005）：HDL胆固醇浓度低的个体中ADRB3的190T→C（Trp64Arg）多态性；HDL胆固醇浓度高的个体中GP1BA的1018C→T（Thr145Met）多态性、AKAP10的A→G（Ile646Val）多态性和UCP3的-55C→T多态性；LDL胆固醇浓度低的个体中F3的-603A→G多态性和ADIPOQ的-11377C→G多态性；TG浓度低的个体中GP1BA的1018C→T多态性；TG浓度高的个体中PAI1的4G→5G多态性。在LDL胆固醇浓度高的个体中，没有多态性与MI相关。这些结果表明，与MI相关的多态性在不同血脂谱的个体中可能有所不同。因此，根据血脂谱对受试者进行分层对于基于遗传信息的MI个性化预防可能很重要。
