Correlations between plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and PAF-AH genotype, age, and atherosclerosis in a Japanese population
Correlations between plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and PAF-AH genotype, age, and atherosclerosis in a Japanese population
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DOI：
10.1016/s0021-9150(99)00385-8
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发表时间：
2000-05-01
期刊：
影响因子：
5.3
通讯作者：
Yokota, M
中科院分区：
文献类型：
--
作者：
Yamada, Y;Yoshida, H;Yokota, M
血小板活化因子乙酰水解酶（PAF-AH）是一种水解PAF和氧化磷脂的血浆酶，被认为参与保护细胞免受氧化应激。血浆PAF-AH基因中的G（994）（M等位基因）-> T（m等位基因）突变导致成熟蛋白中的瓦尔（279）-> Phe取代，导致催化活性丧失。为了阐明PAF-AH酶活性、基因型、年龄和动脉粥样硬化之间的关系，我们在一个大的日本人群中检测了这些参数（n = 3932），包括三组;对照组（健康个体; n = 1684），风险因素组（具有至少一种动脉粥样硬化的常规危险因素的个体; n=1398）和患病组（患有心肌梗塞或中风的患者; n = 850）。我们观察到，与对照组或危险因素组相比，患病组中m等位基因的频率显著增加。血浆PAF-AH活性随着年龄的增长显着增加，在妇女与MM和Mm基因型的对照组，在男性与MM基因型的对照组，但不是在男性与Mm基因型。然而，在危险因素组和患病组中，在具有任一基因型的受试者中，血浆PAF-AH活性与年龄之间没有观察到相关性。这些结果表明，在具有MM基因型的个体中，血浆PAF-AH活性可能会增加，以响应可能随年龄积累的PAF和/或氧化磷脂诱导的应激，但这种反应在具有m基因型的健康个体中并不明显或减少。等位基因，或患有动脉粥样硬化疾病或有危险因素的受试者。结合我们以前的发现，PAF-AH基因的G（994）->T突变可能是日本人群动脉粥样硬化疾病的遗传决定因素之一。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
Platelet-activating factor acetylhydrolase (PAF-AH), a plasma enzyme that hydrolyzes PAF and oxidized phospholipids, is thought to be involved in protecting cells against oxidative stress. A G(994) (M allele)--> T (m allele) mutation in the plasma PAF-AH gene, which results in a Val(279) --> Phe substitution in the mature protein, leads to a loss of catalytic activity. To elucidate the relationships among PAF-AH enzyme activity, genotype, age, and atherosclerosis, we assayed these parameters in a large Japanese population (n = 3932) that consisted of three groups; a control group (healthy individuals; n = 1684), a risk-factor group (individuals having at least one conventional risk factor for atherosclerosis; n=1398), and a diseased group (patients who had suffered a myocardial infarction or stroke; n = 850). We observed a significantly increased frequency of the m allele in the diseased group as compared with the control or risk-factor groups. Plasma PAF-AH activity increased significantly with age in women in the control group with the MM and Mm genotypes, and in men in the control group with the MM genotype, but not in men with the Mm genotype. In both the risk-factor and diseased groups, however, no correlation was observed between plasma PAF-AH activity and age in subjects with either genotype. These results suggest that in individuals with the MM genotype, plasma PAF-AH activity may be increased in response to stresses induced by PAF and/or oxidized phospholipids that might accumulate with age, but that this response is not evident or reduced in healthy individuals with the m allele, or in subjects with atherosclerotic disease, or having risk factors. Together with our previous findings, the G(994)-->T mutation in the PAF-AH gene may be one of the genetic determinants for atherosclerotic disease in the Japanese population. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.