Mackness Mike, Durrington Paul, Mackness Bharti
University Department of Medicine, Manchester Royal Infirmary, Manchester, UK.
Curr Opin Lipidol. 2004 Aug;15(4):399-404. doi: 10.1097/01.mol.0000137227.54278.29.
To provide up-to-date information on the most recent advances in the epidemiology, biochemistry and molecular biology of the antiatherosclerotic enzyme paraoxonase 1.
Case-control and prospective studies published during the period covered by this review have indicated that paraoxonase 1 'status' (i.e. activity and/or concentration) was a more important coronary heart disease risk factor than the paraoxonase 1 genetic polymorphisms. New findings on the role of paraoxonase 1 in homocysteine metabolism are reviewed, as are advances in the nutritional and pharmacological regulation of paraoxonase 1. The recent controversy over whether paraoxonase 1 or platelet-activating factor acetylhydrolase is responsible for the antioxidant activity of high-density lipoprotein is also addressed.
In the light of recent findings, we believe that genetic epidemiological studies of the paraoxonase 1 polymorphisms in relation to coronary heart disease should no longer be undertaken unless they are very large and prospective in nature. More research should be undertaken to discover the biochemical mechanisms underlying the mode of action of paraoxonase 1 and the factors which modulate its activity and/or concentration.
Bharti Mackness is funded by the International HDL Research Awards Programme. All authors receive research funding from the British Heart Foundation and Diabetes UK.
提供有关抗动脉粥样硬化酶对氧磷酶1在流行病学、生物化学和分子生物学方面最新进展的最新信息。
在本次综述涵盖期间发表的病例对照研究和前瞻性研究表明,对氧磷酶1“状态”(即活性和/或浓度)是比其基因多态性更重要的冠心病危险因素。文中回顾了对氧磷酶1在同型半胱氨酸代谢中作用的新发现,以及对氧磷酶1营养和药理调节方面的进展。还讨论了近期关于对氧磷酶1还是血小板活化因子乙酰水解酶负责高密度脂蛋白抗氧化活性的争议。
鉴于最近的发现,我们认为除非是大规模的前瞻性研究,否则不应再开展关于对氧磷酶1基因多态性与冠心病关系的遗传流行病学研究。应开展更多研究以发现对氧磷酶1作用方式的生化机制以及调节其活性和/或浓度的因素。
巴尔蒂·麦克尼斯由国际高密度脂蛋白研究奖励计划资助。所有作者均获得英国心脏基金会和英国糖尿病协会的研究资金。