Tobacco smoking modifies association between Gln-Arg192 polymorphism of human paraoxonase gene and risk of myocardial infarction
Tobacco smoking modifies association between Gln-Arg192 polymorphism of human paraoxonase gene and risk of myocardial infarction
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DOI：
10.1161/01.atv.20.9.2120
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发表时间：
2000-09-01
影响因子：
8.7
通讯作者：
Campos, H
中科院分区：
文献类型：
--
作者：
Sen-Banerjee, S;Siles, X;Campos, H
对氧磷酶是一种高密度脂蛋白相关的人体血清酶，通过防止脂质过氧化在动脉粥样硬化中发挥作用。其活性受对氧磷酶基因(PON1)第192位(Gln--&Gt；Arg)和55位(Met--&Gt；Leu)两个常见氨基酸多态的调控。我们在一项基于人群的研究中研究了PON1基因多态性与心肌梗死(MI)的关系，该研究包括492例病例和518名对照，这些病例与年龄、性别和居住地相匹配，均居住在哥斯达黎加。病例组PON1(192Arg)等位基因频率(0.27)高于对照组(0.24，P=0.008)，而PON1(55Leu)的等位基因频率(0.26)无显著差异。与PON1(192Gln-Gln)等位基因相比，PON1(192Arg)等位基因与心肌梗死的风险增加相关(优势比[OR]1.36，CI 1.06至1.75)，且这种关联独立于PON1(55)基因多态性，PON1(55)与MI无关(OR 1.10，CI 0.82至1.48)。调整血脂和非血脂危险因素后，PON1(192Arg)与心肌梗死风险之间的关联得到加强(OR1.51，CI 1.13至2.03)。有趣的是，这种关联只在非吸烟者中明显(OR 1.90，CI 1.29至2.79)：没有证据表明吸烟者之间存在关联(OR 0.95，CI 0.57至1.79)。PON1(192)与吸烟状况的交互作用有统计学意义(P=0.04)。因此，PON1(192)基因多态而不是PON1(55)基因多态与心肌梗死的风险增加相关。这种联系在吸烟者中并不明显。
Paraoxonase, a high density lipoprotein-associated human serum enzyme, plays a role in atherosclerosis by protecting against lipid peroxidation. Its activity is modulated by 2 common amino acid polymorphisms at positions 192 (Gln-->Arg) and 55 (Met-->Leu) in the paraoxonase gene (PON1). We studied the association of PON1 polymorphisms and myocardial infarction (MI) in a population-based study consisting of 492 cases and 518 controls matched for age, sex,and area of residence, all living in Costa Rica. The allele frequency of PON1(192Arg) was higher in cases (0.27) than in controls (0.24, P=0.008), whereas that of PON1(55Leu) was identical (0.26). Compared with PON1(192Gln-Gln), the PON1(192Arg) allele was associated with an increased risk of MI (odds ratio [OR] 1.36, CI 1.06 to 1.75), and this association was independent of the PON1(55) polymorphism, which was not associated with MI (OR 1.10, CI 0.82 to 1.48). Adjustment for lipid and nonlipid risk factors strengthened the association between PON1(192Arg) and the risk of MI (OR 1.51, CI 1.13 to 2.03). Interestingly, this association was evident only among nonsmokers (OR 1.90, CI 1.29 to 2.79): there was no evidence of an association in smokers (OR 0.95, CI 0.57 to 1.79). The interaction between PON1(192) and smoking status was statistically significant (P=0.04). Thus, the PON1(192) but not the PON1(55) gene polymorphism is associated with an increased risk of MI. This association is not evident among smokers.