Laboratory Diagnosis Center, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
BMC Med Genet. 2013 Jan 28;14:16. doi: 10.1186/1471-2350-14-16.
The human paraoxonase (PON) gene family has three isoforms: PON1, PON2 and PON3. These genes are implicated as potential risk factors of cerebrovascular disease and can prevent oxidative modification of low-density lipoproteins and atherosclerosis. This study evaluated the association between the genetic variants of all three PON genes and the risks of total stroke, ischemic stroke and hemorrhagic stroke in the Han Chinese population.
A total of 1016 subjects were recruited, including 508 healthy controls and 498 patients (328 with ischemic stroke and 170 with hemorrhagic stroke). A total of 11 single nucleotide polymorphisms (SNPs) covering the PON genes were genotyped for statistical analysis. Two of the 11 SNPs (rs662 and rs854560) were contextualized in a meta-analysis of ischemic stroke.
The presence of rs705381 (-162) in the promoter region of PON1 was significantly associated with total stroke (P(adjusted) = 0.0007, OR = 0.57 [95% CI = 0.41-0.79]) and ischemic stroke (P(adjusted) = 0.0017, OR = 0.54 [95% CI = 0.37-0.79]) when analyzed using a dominant model, but was not associated with hemorrhagic stroke. There was also a nominal association between rs854571 (-824) and total stroke. Meta-analysis demonstrated a significant nominal association between rs662 and ischemic stroke, but there was no evidence of an association between rs662 and ischemic stroke risk in a single site association study.
These findings indicate that polymorphisms of PON1 gene may be a risk factor of stroke.
人对氧磷酶（PON）基因家族有三种同工酶：PON1、PON2 和 PON3。这些基因被认为是脑血管病的潜在危险因素，可以防止低密度脂蛋白的氧化修饰和动脉粥样硬化。本研究评估了三种 PON 基因的遗传变异与汉族人群总卒中、缺血性卒中和出血性卒中风险的关系。
共纳入 1016 例受试者，包括 508 例健康对照者和 498 例患者（328 例缺血性卒中和 170 例出血性卒中）。对所有 PON 基因的 11 个单核苷酸多态性（SNP）进行基因分型，用于统计分析。其中两个 SNP（rs662 和 rs854560）在缺血性卒中的荟萃分析中进行了定位。
PON1 启动子区域 rs705381（-162）的存在与总卒中（调整后 P=0.0007，OR=0.57[95%CI=0.41-0.79]）和缺血性卒中（调整后 P=0.0017，OR=0.54[95%CI=0.37-0.79]）显著相关，当采用显性模型分析时，但与出血性卒中无关。rs854571（-824）与总卒中也存在名义关联。荟萃分析显示 rs662 与缺血性卒中存在显著的名义关联，但在单部位关联研究中，没有证据表明 rs662 与缺血性卒中风险有关。
这些发现表明 PON1 基因多态性可能是卒中的一个危险因素。
