Ruiz J, Blanché H, James R W, Garin M C, Vaisse C, Charpentier G, Cohen N, Morabia A, Passa P, Froguel P
Division d'Epidémiologie Clinique, Geneva University Hospital, Switzerland.
Lancet. 1995 Sep 30;346(8979):869-72. doi: 10.1016/s0140-6736(95)92709-3.
Paraoxonase is a high-density-lipoprotein-associated enzyme capable of hydrolysing lipid peroxides. Thus it might protect lipoproteins from oxidation. It has two isoforms, which arise from a glutamine (A isoform) to arginine (B isoform) interchange at position 192. The relevance of this polymorphism to coronary heart disease (CHD) in non-insulin-dependent diabetic patients was investigated in case-control study. Of the 434 patients, 171 had confirmed coronary artery disease; the other 263 had no history of such disease. The B allele and AB+BB genotypes were associated with an increased risk of coronary heart disease. Compared with subjects homozygous for the A allele (AA genotype), the odds ratio of CHD for subjects homozygous for the B allele was 2.5 (95% CI 1.2-5.3) and that for those heterozygous for the B allele was 1.6 (95% CI 1.1-2.4), suggesting a codominant effect on cardiovascular risk. When subjected to multivariate analysis, the B allele remained significantly associated with CHD (odds ratio 1.94, p = 0.03). The paraoxonase gene polymorphism is thus an independent cardiovascular risk factor in non-insulin-dependent diabetic patients. A possible explanation for this finding is that activity of the paraoxonase B isotype does not protect well against lipid oxidation, a major atherogenic pathway.
对氧磷酶是一种与高密度脂蛋白相关的酶，能够水解脂质过氧化物。因此，它可能保护脂蛋白免于氧化。它有两种同工型，由192位的谷氨酰胺（A同工型）与精氨酸（B同工型）互换产生。在一项病例对照研究中，调查了这种多态性与非胰岛素依赖型糖尿病患者冠心病（CHD）的相关性。在434名患者中，171人确诊患有冠状动脉疾病；另外263人无此类疾病史。B等位基因以及AB + BB基因型与冠心病风险增加相关。与A等位基因纯合子（AA基因型）的受试者相比，B等位基因纯合子受试者患冠心病的比值比为2.5（95%置信区间1.2 - 5.3），B等位基因杂合子受试者的比值比为1.6（95%置信区间1.1 - 2.4），提示对心血管风险有共显性效应。进行多变量分析时，B等位基因仍与冠心病显著相关（比值比1.94，p = 0.03）。因此，对氧磷酶基因多态性是非胰岛素依赖型糖尿病患者独立的心血管危险因素。对这一发现的一种可能解释是，对氧磷酶B同种型的活性不能很好地抵御脂质氧化，而脂质氧化是主要的致动脉粥样硬化途径。
