机构：[a]Departments of Neurology,Xuan Wu Hospital,Capital Medical University, Beijing , China神经内科首都医科大学宣武医院[b]Departments of Cardiology,Xuan Wu Hospital,Capital Medical University, Beijing , China心脏科（内科专业）首都医科大学宣武医院
Background: Despite accumulating evidence supporting the association between variants of the ALOX5AP gene and atherosclerotic vascular events, the precise mechanism is still unclear. No variants in the coding sequence that lead to amino acid substitution have been found. We investigated genetic variants in the promoter region of the ALOX5AP gene and the association with ischemic stroke in a north Chinese Han population. Methods: 505 cases of ischemic stroke and 500 age- and gender-matched controls of the north Chinese Han population were enrolled. Genetic variants in the promoter region of the ALOX5AP gene were identified by polymerase chain reaction and DNA sequencing. 40 cases and 40 controls were randomly selected and compared for serum leukotriene B(4) (LTB(4)) concentration. The effect on ischemic stroke was evaluated by logistic regression. Results: Three genetic variants were identified, including a mutation (-519 G > A), an insertion and deletion polymorphisms (-581_582 Ins A) and a single nuclear polymorphisms (-946 A > G). Association study showed that the II genotype of -581_582 Ins A was significantly associated with ischemic stroke of a large artery atherosclerosis (OR = 3.50, 95% CI = 1.93-6.36, p = 0.0002) and undetermined etiology (OR = 3.66, 95% CI = 1.92-6.94, p = 0.0006). No significant association was found between the -519 GA genotype (OR = 0.35, 95% CI = 0.02-5.88, p = 0.46), -946 AG genotype (OR = 1.35, 95% CI = 0.85-2.16, p = 0.21) and ischemic stroke. There was no significant difference in serum LTB(4) concentration between cases (n = 40) and controls (n = 40) (log serum LTB(4) of cases vs. controls: 2.67 +/- 0.14 vs. 2.73 +/- 0.18 pg/ml, p = 0.10). However, the serum LTB(4) concentration was significantly higher in participants with the II genotype of -581_582 Ins A (n = 12) than that of participants with the DD genotype (n = 68) (log serum LTB(4) of participants with II genotype vs. DD genotype: 2.82 +/- 0.18 vs. 2.68 +/- 0.15 pg/ml, p = 0.01). Conclusion: The -581_582 Ins A polymorphism might be a novel genetic risk factor for ischemic stroke in a north Chinese Han population. Further studies on molecular mechanism are warranted. Copyright (C) 2011 S. Karger AG, Basel
基金：
National Nature Science Foundation of China (30700240)
the Nova Program of Beijing Science and Technology Commission (2008B30)
第一作者机构：[a]Departments of Neurology,Xuan Wu Hospital,Capital Medical University, Beijing , China[*1]Department of Neurology, Xuan Wu Hospital Capital Medical University Beijing 100053 (China)
通讯作者：
通讯机构：[*1]Department of Neurology, Xuan Wu Hospital Capital Medical University Beijing 100053 (China)
推荐引用方式(GB/T 7714)：
Ruijun Ji,Jianping Jia,Xin Ma,et al.Genetic Variants in the Promoter Region of the ALOX5AP Gene and Susceptibility of Ischemic Stroke[J].CEREBROVASCULAR DISEASES.2011,32(3):261-268.doi:10.1159/000330341.
APA：
Ruijun Ji,Jianping Jia,Xin Ma,Jian Wu,Yanli Zhang&Liqing Xu.(2011).Genetic Variants in the Promoter Region of the ALOX5AP Gene and Susceptibility of Ischemic Stroke.CEREBROVASCULAR DISEASES,32,(3)
MLA：
Ruijun Ji,et al."Genetic Variants in the Promoter Region of the ALOX5AP Gene and Susceptibility of Ischemic Stroke".CEREBROVASCULAR DISEASES 32..3(2011):261-268
