Department of Biochemistry, Institute of Natural and Applied Sciences, Middle East Technical University, Ankara, Turkey.
Cell Biochem Funct. 2009 Dec;27(8):558-67. doi: 10.1002/cbf.1607.
Paraoxonase1 (PON1) is protective against the development of atherosclerosis, a risk factor for ischemic stroke. PON1 gene has one promoter region (-107T/C) and two coding region (192Q/R and 55L/M) polymorphisms that affect the levels and catalytic efficiency of the enzyme, respectively. In this study, we aimed to determine the importance of -107T/C, 192Q/R and 55L/M polymorphisms of PON1 gene and three PON1 activities (diazoxonase, paraoxonase, arylesterase) as risk factors for ischemic stroke.
Study population was comprised of 172 unrelated adult Caucasian patients with acute hemispheric ischemic stroke and 105 symptom-free controls. Genotypes were attained by PCR followed by restriction enzyme digestion and phenotypes were determined by spectrophotometric assays.
This is the first study analyzing diazoxonase activity as a risk factor for ischemic stroke. Nevertheless, diazoxonase, paraoxonase and arylesterase activities were almost the same in stroke patients and controls. The -107TT genotype was associated with a 1.97 times increased risk for stroke in elderly (age > 59). Individuals with this genotype were found to have the lowest PON1 enzyme activities among the -107T/C genotypes. Triple combined haplotype QRLMTC was found to be 6.94- and 10.4-times protective against ischemic stroke in the overall and the elderly population, respectively. 55LL genotype was associated with a 1.78-fold increase in the risk of ischemic stroke.
PON1 genotypes, but not activities, are related with the risk of stroke.
对氧磷酶 1（PON1）可预防动脉粥样硬化的发生，而动脉粥样硬化是缺血性中风的一个危险因素。PON1 基因有一个启动子区域（-107T/C）和两个编码区域（192Q/R 和 55L/M）多态性，分别影响酶的水平和催化效率。在这项研究中，我们旨在确定 PON1 基因的-107T/C、192Q/R 和 55L/M 多态性以及三种 PON1 活性（对氧磷酶、对氧磷酶、芳基酯酶）作为缺血性中风危险因素的重要性。
研究人群由 172 名无关联的成年白种人急性半球性缺血性中风患者和 105 名无症状对照者组成。通过聚合酶链反应（PCR）后用限制性内切酶消化获得基因型，通过分光光度法测定表型。
这是第一项分析对氧氮杂环戊烷酶活性作为缺血性中风危险因素的研究。然而，在中风患者和对照组中，对氧氮杂环戊烷酶、对氧磷酶和芳基酯酶的活性几乎相同。-107TT 基因型与老年（年龄＞59 岁）中风风险增加 1.97 倍相关。在-107T/C 基因型中，发现该基因型个体的 PON1 酶活性最低。QLRMTC 三重组合单倍型在总体人群和老年人群中分别对缺血性中风具有 6.94 倍和 10.4 倍的保护作用。55LL 基因型与缺血性中风风险增加 1.78 倍相关。
PON1 基因型而非活性与中风风险相关。
