华东地区ALOX5AP基因单核苷酸多态性与缺血性脑卒中的相关性研究

Association of ALOXSAP with ischemic stroke among eastern Chinese Han population

目的 探讨5-脂氧合酶激活蛋白（ALOX5AP）基因多态性位点与中国华东地区汉族人群缺血性脑卒中的相关性.方法 本研究共纳入658例缺血性脑卒中患者,704例健康者做对照研究,并进一步将病例组进行TOAST分型,采用Taqman探针技术检测基因多态性.运用统计软件进行基因型、等位基因等关联分析,以及基因多态性与缺血性脑卒中及其亚型之间患病风险的独立相关性分析.结果 rs17222919位点突变与华东地区缺血性脑卒中的发生成正相关.rs17222919 TG型能显著升高缺血性脑卒中的发病风险（OR=1.34,95%CI=1.02～1.75）,尤其与小动脉闭塞型（SAO）脑卒中发病密切相关（OR=1.40,95%CI=1.02～1.93）.TG和TG/GG型能显著增加女性脑卒中的发病风险,并经传统危险因素高血压分层后,同样能够显著增加高血压人群患脑卒中风险.而rs9579646位点经过性别分层后,AG和AG/GG型能降低男性缺血性脑卒中的发病风险,并且按照传统危险因素分层后,AG型能降低非高血压人群脑卒中的发病风险.结论 ALOX5AP多态性与中国华东地区汉族人群缺血性脑卒中患者密切相关,提示该基因多态性可能参与了中国华东地区汉族人群缺血性脑卒中的发生.

Objective To investigate the possible relationship between single nucleotide polymorphisms （SNPs） in ALOXSAP gene and ischemic stroke in eastern Han population of China. Methods 658 cases and 704 controls were recruited, and then were divided by the Trial of Org 10172 in Acute Stroke Treatment （TOAST）. Taqman were used for target gene genotyping and SNPs analysis. Association study was performed to analyze the relationship between genotype and phenotype and the multivariate Logistic regression was adopted to adjust the bias of conventional stroke risk factors. Results The genotype frequencies of TG of the SNPs rs17222919 located in the promoter of ALOXSAP gene were significantly higher in ischemic stroke patients than controls（ OR = 1.34, 95% CI = 1.02 - 1.75 ）, especially in stroke caused by small - artery occlusion （SAO） （ OR = 1.40, 95% CI = I. 02 - 1.93 ）. Meanwhile, the genotype frequencies of TG and TG/GG in female were higher in cases than in controls. After specification, the genotype frequencies of TG and TG/GG were higher in cases than in controls with hypertension. The genotype frequencies of AG and AG/GG of the SNPs 9579646 located in the intron of ALOXSAP gene were higher in controls than in cases. After specification, the genotype frequencies of TG were higher in controls than in cases without hypertension. Conclusion The SNPs of ALOXSAP zene are closely associated with ischemic stroke in eastern Chinese Han population.