Quality, function and genetic assessments of NO, ACE and HDL in patients with coronary artery disease

冠状动脉疾病患者 NO、ACE 和 HDL 的质量、功能和遗传评估

• 批准号: 09670773
• 负责人: SAKU Keijiro
• 金额: $ 2.3万
• 依托单位: Fukuoka 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670773/
• 关键词: high density lipoprotein; nitric oxide; ACE; gene polymorphism; coronary artery disease; 高比重リポ蛋白(HDL); アンジオテンシン変換酵素; アンジオテンジン変換酵素

1. The fractional esterification rate of cholesterol (C) in apolipoprotein B-depleted plasma (FERィイD2HDLィエD2) is a functional assay of high density lipoprotein (HDL). In the case-control study [with/without angiographically defined coronary artery disease (CAD)], we found that high FERィイD2HDLィエD2 was associated with an increased risk of CAD. The association between FERィイD2HDLィエD2 and CAD was not eliminated by adjusting for potential confounders and HDL-C levels, and the interaction between FERィイD2HDLィエD2 and HDL-C was significant. FERィイD2HDLィエD2 is an independent risk factor for CAD and the combination of FERィイD2HDLィエD2 and HDL-C could be a potent indicator for CAD.2. The association among insulin resistance, as assessed by the homeostasis model assessment, HDL-C, and CAD was investigated in a case-control study. Cases were patients with angiographically defined CAD and controls were matched with cases with regard to gender and age. Cases were characterized by hyperinsulinemia and norm … More al glucose tolerance. Multivariate conditional logistic regression analysis indicated that insulin resistance and HDL-C were independently associated with CAD, but a much stronger association was found between hyperinsulinemic hypoalphalipoproteinemia and CAD. Low HDL-C and hyperinsulinemia synergistically increased the risk of CAD.3. Both nitric oxide (NO) and angiotensin converting enzyme (ACE) play important roles in maintaining endothelium-dependent relaxation/contraction, and in inhibiting/activating cell proliferation, adhesion and chemotaxis. We screened the missense Glu298Asp variant of the eNOS gene and ACE I/D polymorphism in 1002 patients with/without CAD. In diabetic patients, none of the combinations of eNOS and ACE gene polymorphism were related to CAD, while in non-DM patients (n=727), the combination of the missense Glu298Asp variant (TT+TG) and the ACE-DD genotype was found to be a significant predictor of CAD, and other genotypic combinations were not. The combination of the missense Glu298Asp eNOS variant with the ACE-DD genotype may be a marker of CAD in non-DM patients.4. The association between ACE gene polymorphism and insulin resistance (IR) was investigated in patients with angina pectoris. Patients with the ACE-ID genotype had significantly lower IR, as assessed by an oral glucose tolerance test (OGTT) and by homeostatic model assessment (HOMA), compared to those with the ACE-II genotype. Patients were divided into two groups with low and high HOMA-IR, and the I allele was seen more frequently in the high HOMA-IR group than in the low HOMA-IR group. Logistic regression analysis showed that the odds ratio for insulin resistance in patients with the II genotype, compared to those with the ID and DD genotypes, was 4.0, with and without adjusting for the presence of significant coronary atheroscierosis. The patients with the ID and DD genotypes were associated with a significantly lower risk of insulin resistance, compared to those with the II genotype. Less

1.载脂蛋白B耗竭血浆中胆固醇（C）的酯化率（FER β D2 HDL β D2）是高密度脂蛋白（HDL）的功能测定。在病例对照研究[有/无血管造影确诊的冠状动脉疾病（CAD）]中，我们发现高FER胆固醇D2 HDL胆固醇D2与CAD风险增加相关。通过调整潜在的混杂因素和HDL-C水平，并不能消除FER受体D2 HDL受体D2和CAD之间的相关性，FER受体D2 HDL受体D2和HDL-C之间的相互作用是显著的。结论：1.血清FER-D2 HDL-D2是冠心病的独立危险因素，血清FER-D2 HDL-D2和HDL-C联合检测可作为冠心病的有效指标。在一项病例对照研究中，研究了胰岛素抵抗（通过稳态模型评估）、HDL-C和CAD之间的关系。病例为血管造影确诊的CAD患者，对照组与性别和年龄相匹配。2例以高胰岛素血症为特征， ...更多信息 葡萄糖耐量多因素条件Logistic回归分析显示，胰岛素抵抗和高密度脂蛋白胆固醇与冠心病独立相关，而高胰岛素血症、低血脂蛋白血症与冠心病的相关性更强。低HDL-C和高胰岛素血症协同增加CAD的风险。一氧化氮（NO）和血管紧张素转换酶（ACE）在维持内皮依赖性舒张/收缩、抑制/激活细胞增殖、粘附和趋化中起重要作用。我们在1002例患有/不患有CAD的患者中筛查了eNOS基因的错义Glu 298 Asp变体和ACE I/D多态性。在糖尿病患者中，eNOS和ACE基因多态性的组合均与CAD无关，而在非糖尿病患者（n=727）中，错义Glu 298 Asp变异（TT+TG）和ACE-DD基因型的组合被发现是CAD的显著预测因子，而其他基因型组合则不是。错义Glu 298 AspeNOS变异与ACE-DD基因型的联合可能是非DM患者CAD的标志物.目的探讨心绞痛患者血管紧张素转换酶（ACE）基因多态性与胰岛素抵抗（IR）的关系。通过口服葡萄糖耐量试验（OGTT）和稳态模型评估（HOMA），ACE-ID基因型患者的IR显著低于ACE-II基因型患者。将患者分为低HOMA-IR组和高HOMA-IR组，高HOMA-IR组中I等位基因的频率高于低HOMA-IR组。Logistic回归分析显示，与ID和DD基因型患者相比，II基因型患者胰岛素抵抗的比值比为4.0，有或没有校正显著的冠状动脉粥样硬化的存在。与II基因型患者相比，ID和DD基因型患者的胰岛素抵抗风险显著降低。少

项目成果

Saku K., Zhang B., et al.: "Associations among serum lipoprotein(a) [Lp(a)] levels, apolipoprotein(a) phenotypes, and myocardial infarction in patients with extremely low and high serum levels of Lp(a)"Jpn Circ J. 63. 659-665 (1999)

Saku K.、Zhang B. 等人：“血清 Lp(a) 水平极低和极高的患者的血清脂蛋白 (a) [Lp(a)] 水平、载脂蛋白 (a) 表型与心肌梗死之间的关联

Saku K.,Zhang B.,et al.: "Associations among serum lipoprotein(a)[Lp(a)]levels,apolipoprotein(a)phenotypes,and myocardial infarction in patients with extremely low and high serum levels of Lp(a)."Jpn Circ J. 63. 659-665 (1999)

Saku K.，Zhang B.，et al.：“血清脂蛋白（a）[Lp（a）]水平、载脂蛋白（a）表型与血清 Lp（a）水平极低和极高的患者中的心肌梗死之间的关联

Bai H.,Saku K.,et.al.: "Polymorphism of the apolipoprotein A-IV gene and its significance in lipid metabolism and coroanry heart disease in a Japanese population." Europ J Clin Invest.26. 1115-1124 (1996)

Bai H.，Saku K.，et.al.：“载脂蛋白 A-IV 基因的多态性及其在日本人群脂质代谢和冠心病中的意义。”

Saku K.,von Eckardstein A.,Zhang B.,Liu R.,Jimi S.,Ou JF.,Ohta T.Assmann G.,Arakawa K.: "In vivo kinetics of human apolipoprotein A-I variants in rabbits."Europ J Clin Invest. 29. 196-203 (1998)

Saku K.、von Eckardstein A.、Zhang B.、Liu R.、Jimi S.、Ou JF.、Ohta T.Assmann G.、Arakawa K.：“人载脂蛋白 A-I 变体在兔体内的体内动力学。”Europ

Kiyonaga A., Imai K., Zhang B., Saku K.: "Exercise Prevent Comm Dis"Springer-Verlag. 10 (1999)

Kiyonaga A.、Imai K.、Zhang B.、Saku K.：“Exercise Prevent Comm Dis”Springer-Verlag。