| Project/Area Number |
09670773
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Fukuoka University |
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Principal Investigator |
SAKU Keijiro Fukuoka Univ. Sch. of Medicine, Lecturer, 医学部, 講師 (40183371)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAGAI Kouichiro Fukuoka Univ. Sch. of Med., Lecturer, 医学部, 講師 (10248510)
OHTA Takao Ryukyu Univ. Sch. of Medicine, Professor, 医学部, 教授 (70185271)
JIMI Shiro Fukuoka Univ. Sch. of Med., Assist. Prof., 医学部, 助手 (30226360)
TASHIRO Eiichiro Fukuoka Univ. Sch. of Med., Assist. Prof., 医学部, 助手 (20271439)
SHIRAI Kazuyuki Fukuoka Univ. Sch. of Med., Assist. Prof., 医学部, 助手 (80268995)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | 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 |
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| Research Abstract |
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
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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
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