5-脂氧合酶激活蛋白基因多态性增加阿司匹林抵抗易感性

Polymorphisms of ALOX5AP gene increase susceptibility of aspirin resistance

目的探讨5-脂氧合酶激活蛋白（ALOX5AP）基因单核苷酸多态性与中国汉族人群阿司匹林抵抗（AR）的相关性。方法纳入450例持续服用阿司匹林（100mg,≥7d）的缺血性心脑血管病中的高危患者,血栓弹力图检测花生四烯酸途径的血小板聚集率,依据诊断标准分为AR组110例,阿司匹林敏感（AS）组340例。聚合酶链反应-限制性片段长度多态性技术分析SG13S32、SG13S89和SG13S114单核苷酸多态性。应用Haploview软件构建单倍型,并进行分析。结果 AR组与AS组SG13S114T/A突变A等位基因频率分布（40.5%vs 31.3%,P=0.01）和AA/TA基因型及TT基因型比较,差异有统计学意义（35.5%vs 46.2%,P=0.03）。而2组SG13S89、SG13S32基因型和等位基因分布频率比较,差异无统计学意义（P〉0.05）。logistic回归分析显示,携带SG13S114AA/TA基因型的人群发生AR的风险是携带TT基因型的3.241倍（95%CI：1.552~6.767,P=0.002）。单倍型分析显示,TG是1种危险单倍型,携带TG单倍型的人群AR发生风险是不携带TG单倍型人群的1.490倍（95%CI：1.088~2.040,P=0.014）,AG是1种保护单倍型,可以减少AR发生的风险（OR=0.691,95%CI：0.502~0.952,P=0.029）。结论 ALOX5AP rs10507391与汉族人群AR相关;危险单倍型TG可增加AR发生风险。

Objective To study the association between SNP of ALOX5 AP gene and susceptibility of aspirin resistance（AR）in Chinese Han population.Methods Four hundred and fifty patients at high risk of ischemic cardiocerebral vascular disease on aspirin therapy（100mg/d,≥7days）were divided into aspirin resistant（AR）group（n=110）and aspirin sentivie（AS）group（n=340）.Polymorphisms of the ALOX5 AP gene（SG13S114,SG13S89,SG13S32）were detected by PCR-RFLP.A haplopty model was established using Haploview.Results The frequency of mutated SG13S114T/A at allele A was significantly higher and that at genotypes AA/TA and TT was significantly lower in AR group than in AS group（40.5%vs 31.3%,P=0.01;35.5%vs 46.2%,P=0.03）.No significant difference was found in the distribution of SG13S89 and SG13S32genotypes and allele gene（P〉0.05）.The risk to develop AR was 3.241-folod higher in SG13S114AA/TA genotype carriers than in TT gemotype carriers（95%CI：1.552-6.767,P=0.002）.Haplotype analysis showed that TG was a risk haplotype and the risk to develop AR was 1.490-fold higher in TG haplotype carriers than in non-TG haplotype carriers（95%CI：1.088-2.040,P=0.014）,AG was a protective haplotype and could reduce the risk to develop AR（OR=0.691,95%CI：0.502-0.952,P=0.029）.Conclusion ALOX5 AP rs10507391is associated with AR in Chinese Han people.TG haplotype increases the risk to develop AR.