脂蛋白相关磷脂酶A2基因A379V多态性与TOAST亚型的关系

Association between Lp-PLA2 Gene A379V Polymorphism and TOAST Classification

目的探讨脂蛋白相关磷脂酶A2(lipoprotein associated phospholipase A2,Lp-PLA2)血清水平及其基因A379V多态性与低分子肝素实验病因分型(the trial of Org 10172 in acute stroke treatment,TOAST)的关系。方法对急性期脑梗死患者(N=200)和对照组(体检中心健康体检者,N=172)应用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清Lp-PLA2水平,聚合酶链反应(polymerasechain reaction,PCR)及基因测序技术检测基因多态性。结果脑梗死组血清Lp-PLA2水平(24.39±6.63)ng/ml,高于对照组(15.78±4.32)ng/ml,差异有显著性(P<0.01);TOAST分型后比较,大动脉粥样硬化性梗死(large artery atherosclerotic stroke,LAA)组、小动脉闭塞性梗死(small artery occlusion stroke,SAO)组、对照组血清Lp-PLA2水平分别是(25.60±6.71)ng/ml、(21.43±5.47)ng/ml、(15.78±4.32)ng/ml,差异有显著性(P<0.01);脑梗死组惠者,Lp-PLA2基因A379V多态性位点CC基因型频率68%,C等位基因频率83%,与对照组的70.9%、84.3%比较,差异无显著性(P>0.05),但是TOAST分型后显示CC纯合子血清Lp-PLA2水平(26.27±6.25)ng/ml较T等位基因携带者(CT+TT)(20.39±5.64)ng/ml发生脑梗死的风险增加(P<0.01)。结论 Lp-PLA2血清水平在脑梗死组升高,LAA组升高最明显;A379V基因多态性CC基因型与脑梗死的发病可能相关。

Objective To explore the relationship between the serum lipoprotein phospholipase A2（Lp- PLA2） level and its gene A379V polymorphism and the trial of Org 10172 in acute stroke treatment（TOAST） subtypes of cerebral infarction. Methods The serum Lp-PLA2 level in 200 patients with acute cerebral infarction and 172 healthy controls were measured by Enzyme linked immunosorbent assay（ELISA）. Polymerase chain reaction（PCR） and direct sequencing assay were used to detect gene polymorphism. Results The serum Lp-PLA2 level of the patients （24.39±6.63）ng/ml was higher than that in healthy controls （15.78±4.32）ng/ml, there was a significant difference（P〈0.01）. According to TOAST classification, we found that serum Lp-PLA2 level was significant different among large artery atherosclerotic stroke（LAA） group （25.60±6.71）ng/ml, small artery occlusion stroke（SAO） group （21.43±5.47）ng/ml and healthy controls （15.78±4.32）ng/ml（P〈0.01）. Among the patients, the CC genotype frequency was 68%,the C allele frequency was 83%,compared with the healthy controls（CC genotype frequency was 68%,C was 83%）, there was no difference（P〉0.05）. However, the serum Lp-PLA2 level of the CC homozygote （26.27±6.25）ng/ml had significantly higher stroke risk compared with the T allele carriers（CT＋TT） （20.39±5.64）ng/ml（P〈0.01）.Conclusion The serum Lp-PLA2 level in the cerebral infarction increased, LAA group was the most obvious; Maybe A3 79V polymorphism CC genotype had relationship with stroke.