ALOX5AP基因启动子区单核苷酸多态性与中国北方汉族人群缺血性卒中的关系

Correlativity between single nucleotide polymorphisms in ALOX5AP promoter gene and ischemic stroke in north Chinese Han population

目的探讨 ALOX5AP 基因启动子区单核苷酸多态性与中国北方汉族人群缺血性脑血管病的相关关系。方法本研究共入选北方汉族脑梗死患者220例,同期年龄与性别匹配的对照组191名。采用聚合酶链反应目的基因扩增和基因直接测序的方法鉴别基因型和单核苷酸多态性分析。病例组和对照组基因型分布差异采用关联分析的方法进行检测。经多元 Logistic 回归方法校正经典血管病危险因素后,分析基因多态性与缺血性卒中的相关关系。结果发现3个 ALOX5AP 启动子区未报道的单核苷酸多态性位点,由这3个位点组成的单体型与缺血性脑血管病的发生明确相关,其中 Hap Ⅰ是一种保护性单体型,可以减少缺血性脑血管病发生(OR 0.54,95% CI 0.408～0.715);而 HapⅡ(OR 2.91,95% CI 1.351～6.239)和 Hap Ⅲ(OR 18.82,95% CI 2.562～138.38)则作为一种危险因素,增加缺血性脑血管病发生的风险。另外,-499和-290位点单核苷酸多态性与全脑动脉粥样硬化密切相关。结论与炎症介质白三烯代谢密切相关的 ALOX5AP 基因启动子区单核苷酸多态性与中国北方汉族人群脑梗死的发生有密切关系。

Objective To investigate the role of single nucleotide polymorphisms （SNPs） of ALOXSAP promoter gene in ischemic stroke susceptibility in north Chinese Han population. Methods A total of 220 ischemic stroke patients of north Chinese Han population and 191 healthy controls that had been matched for age and sex were enrolled in this study. Polymerase chain reaction （PCR） and direct sequencing were used for target gene genotyping and SNPs analysis. Association study was performed to analyze the relationship between genotype and phenotype and logistic regression was adopted to adjust the bias of conventional stroke risk factors. Results Three novel SNPs located in the promoter of ALOXSAP gene were found and frequencies of G/A genotype of - 499 site, G/T genotype of - 290 site and G/G genotype of - 190 site were significantly higher in ischemic stroke patients than controls. Meanwhile, three haplotypes consisted of these SNPs were identified to be correlated with ischemic stroke, including a protective haplotype, Hap Ⅰ （OR 0. 54, 95% CI 0. 408 to 0. 715） , and two risk ones, Hap 11 （OR 2.91, 95% CI 1. 351 to 6. 239） and Hap Ⅲ （OR 18. 82, 95% CI 2. 562 to 138. 38）. Meanwhile, the frequencies of G/A genotype of -499 site, G/T genotype of -290 site, Hap Ⅱ and Hap Ⅲ were significantly higher in ischemic stroke patients with more severe cerebral atherosclerosis indicated by digital subtract angiography. Conclusion Three novel SNPs in promoter of ALOXSAP gene are closely associated with ischemic stroke susceptibility in north Chinese Han population.