趋化因子CXCL16基因A181V多态性与TOAST分型的相关性研究

摘要

Objective To investigate the relationship between chemokine CXC ligand 16(CXCL16) gene A181V polymorphism, serum CXCL16 levels and cerebral infarction subtypes according to the trial of ORG 10172 in acute stroke treatment (TOAST) classification.Methods The polymorphisms of CXCL16 gene A181V were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The serum CXCL16 levels in 74 healthy controls and 177 patients with acute cerebral infarction were measured by Enzyme linked immunosorbent assay(ELISA).Results The serum CXCL16 levels of patients were significant higher than those of healthy eontrols(P<0.001). According to TOAST classification, the patient controls were divided into three groups. Then we found that serum CXCL16 levels were significant different among large artery atherosclerotic stroke(LAA) group, small artery occlusion stroke(SAO) group and healthy controls(P<0.001). Logistic regression revealed that serum CXCL16 levels were an independent risk factor for cerebral infarction(P<0.00l). The CXCL16 gene A181V genotype distribution and allele frequencies showed no differences between patient controls and healthy controls(P>0.05). However, among LAA group, SAO group and healthy controls the AA homozygotes had significantly higher cerebral infarction risk compared with the G allele carriers(GA+GG)(P<0.001). CXCL16 gene A181V polymorphism was associated to serum CXCL16levels(P=0.009).Conclusions Serum CXCL16 level correspond well with CXCL16 gene A181V polymorphism. Anallele may be useful to identify patients at increased risk of Large artery atherosclerotic stroke.%目的 探讨趋化因子CXC配体16 (chemokine CXC ligand 16,CXCL16)基因A181V位点多态性与血清CXCL16水平、脑梗死(cerebral infarction,CI)及急性卒中治疗低分子肝素试验病因分型法(the Trial of Org 10172 in Acute Stroke Treatment,TOAST)分型的关系.方法 采用聚合酶链反应-限制性片段长度多态性方法(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)检测基因型,同时对脑梗死急性期患者(n=177)和对照组(查体中心老年健康查体者,n=74)应用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清CXCL16水平.结果 CI组血清CXCL16水平明显高于对照组(P＜0.001)；按TOAST分型后比较,大动脉粥样硬化性卒中(large artery atherosclerotic stroke,LAA)组、小动脉闭塞性卒中(small artery occlusion stroke,SAO)组及对照组三组之间血清CXCL16水平差异仍有显著统计学意义(P＜0.001)；Logistic回归显示血清CXCL16水平是CI的独立危险因素(P＜0.001).CXCL16基因A181V多态性位点基因型频率及等位基因频率在CI组和对照组之间无显著差异(P＞0.05),但是TOAST分型后显示AA纯合子比G等位基因携带者(GA+GG)发生大动脉粥样硬化性卒中的危险增加(P＜0.001).多元线性回归显示,CXCL16基因A181V多态性与血清CXCL16水平独立相关(P=0.009).结论 CXCL16基因A181V多态性与血清CXCL16水平有关,AA基因型与大动脉粥样硬化性卒中密切相关,A等位基因是大动脉粥样硬化严重程度的重要标志.