Paraoxonase與冠心病之關聯

Paraoxonase Associated with Coronary Heart Disease

動脈粥樣硬化為冠心病及腦中風的主要原因，但其機轉至今仍有未明。實驗室對於細胞培養及動物模式之研究顯示，氧化之損傷可能是一個相當重要之因素。藉由檢驗人類族群中候選相關基因之多形性，1998年Sanghera等人報告了一群相關基因常見的多形性，其中包括一種功能未知之酵素－血清paraoxonase，其在冠心病中屬中度之危險因子，一些先前的基因流行病學研究支持此發現。雖然血清PON1（paraoxonase之基因）在有機磷酸鹽代謝上扮演著重要的角色，是長久以來被公認的事實，但PON1在脂質代謝上的角色則是目前有待探討的新領域。人類PON1可能涉及脂質代謝，尤其是磷脂質代謝；亦有報告描述PON1在LDL磷脂質氧化性代謝的可能角色。逐漸增加的證據，顯示PON1可能為動脈粥狀硬化相關的冠心病危險因子。本文即針對此主題作－回顧性的探討。

Mechanisms contributing to atherosclerosis, the major cause of coronary heart disease and stroke, are not well understood. Experimental studies with cultured cells and animal models have suggested that oxidative damage could be an important contributing factor. Sanghera et. al. [Ⅰ] had studied the polymorphisms of candidate genes in a certain populations, and found out that the common polymorphisms in a clusters of related genes, including that of serum paraoxonase, an enzyme of unknown functions was associated with the risk of coronary heart disease. Several previous genetic epidemiologic studies have also yielded similar results.Although it has long been recognized that serum PON1 plays a pivotal role in organophosphate metabolism, the role of PON1 in lipid metabolism is a relatively new area of investigation. Human PON1 may be involved in lipid metabolism particularly phospholipid metabolism. Some reports described that PON1 may play an important role in LDL, phospholipid peroxide metabolism. However, there are growing evidences to suggest that PON1 is a risk factor for atherosclerosis related coronary heart disease.