Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes
Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes
复制标题
DOI：
10.2337/diabetes.48.3.623
复制
发表时间：
1999-03-01
期刊：
影响因子：
7.7
通讯作者：
Häring, HU
中科院分区：
文献类型：
--
作者：
Pfohl, M;Koch, M;Häring, HU
对氧磷酶是一种HDL相关酶，通过保护脂蛋白免受过氧化作用而参与动脉粥样硬化的发病机制。其192位密码子的双等位基因多态性（谷氨酰胺/精氨酸）与冠状动脉疾病（CAD）相关。为了进一步评估对氧磷酶基因多态性在2型糖尿病中对CAD的作用，我们确定了288例2型糖尿病患者（170例有血管造影证实的CAD，118例无血管造影证实的CAD）的对氧磷酶基因型。对氧磷酶192 Gln/Arg基因型进行了评估，使用聚合酶链反应，然后通过AlwI消化。冠心病组Gin等位基因频率为0.656，对照组为0.746（χ 2 = 5.36，P = 0.02）。与Gln/Gln基因型相比，携带至少一个Arg等位基因的受试者患CAD的年龄调整优势比为1.78（95%CI 1.08-2.96，P = 0.02）。在多变量分析中，在校正了可能的混杂因素年龄、性别、吸烟史和高血压后，这种关联甚至更强。在吸烟者和既往吸烟者中，携带至少一个Arg等位基因的患者患冠心病的OR值为3.58（1.45-9.53，P < 0.01）。对氧磷酶Arg等位基因与心肌梗死病史无关（OR 1.20 [0.73-1.99，NS]），但与CAD程度相关（三支血管病变OR 1.92 [1.15-3.27，P = 0.01]）。我们的数据表明，人类对氧磷酶基因的192精氨酸等位基因是冠心病的危险因素，但不是2型糖尿病患者心肌梗死的危险因素，吸烟进一步修改的危险因素。这种风险可能是由于对氧磷酶Arg亚型保护脂蛋白免受过氧化作用的能力降低。
Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic gene polymorphism at codon 192 (glutamine/arginine) has been associated with coronary artery disease (CAD). To further evaluate the role of this paraoxonase gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase genotype in 288 type 2 diabetic patients (170 with and 118 without angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was assessed using polymerase chain reaction followed by AlwI digestion. The frequency of the Gin allele was 0.656 in the CAD patients and 0.746 in the controls (chi(2) = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age-adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects carrying at least one Arg allele. In the multivariate analysis, this association was even stronger after correction for the possible confounders age, sex, smoking history, and hypertension. Among current and former smokers, the odds ratio (OR) for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P < 0.01). The paraoxonase Arg allele was not associated with the history of myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not myocardial infarction in type 2 diabetic patients, a risk factor further modified by cigarette smoking. This risk could possibly be explained by a reduced ability of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.