吸烟与血小板纤维蛋白原受体糖蛋白IIb/IIIA PlA1/A2多态性在腔隙性卒中风险及中期生存方面存在相互作用。

Smoking and the platelet fibrinogen receptor glycoprotein IIb/IIIA PlA1/A2 polymorphism interact in the risk of lacunar stroke and midterm survival.

作者信息

Oksala Niku K J, Heikkinen Maarit, Mikkelsson Jussi, Pohjasvaara Tarja, Kaste Markku, Erkinjuntti Timo, Karhunen Pekka J

机构信息

Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland.

出版信息

Stroke. 2007 Jan;38(1):50-5. doi: 10.1161/01.STR.0000251719.59141.36. Epub 2006 Nov 30.

DOI:10.1161/01.STR.0000251719.59141.36

PMID:17138951

Abstract

BACKGROUND AND PURPOSE

Smoking, increased fibrinogen levels, and platelet activation are related to the risk of ischemic stroke. The platelet fibrinogen receptor glycoprotein (Gp) IIb/IIIa Pl(A1/A2) polymorphism affects the binding of platelets to fibrinogen and is suggested to interact with smoking.

METHODS

We explored the association of smoking and the Pl(A1/A2) polymorphism with ischemic stroke and survival in the Stroke Aging Memory cohort, comprising 486 consecutive patients (55 to 85 years old) who were analyzed 3 months after an ischemic stroke and followed up for 15 months. Stroke subtype determined by magnetic resonance imaging and GpIIb/IIIa Pl(A1/A2) genotype data were available for 272 patients.

RESULTS

In multivariate analysis, smoking was the only factor related to the risk of lacunar infarcts (odds ratio [OR]=1.87, 95% CI=1.05 to 3.31; P=0.033), and it was also a predictor of death (n=24, 8.8%) at 15 months (OR=5.13, 95% CI=1.61 to 16.36; P=0.006), along with age (OR=1.10, 95% CI=1.01 to 1.19; P=0.008). The GpIIb/IIIa Pl(A1/A2) polymorphism alone showed no association with stroke subtype or survival. However, there was a smoking-by-genotype association with the risk of lacunar infarcts (OR=2.10, 95% CI=0.90 to 4.89; P=0.087) and with survival (OR=2.78, 95% CI=0.89 to 8.61; P=0.077). Among younger (55 to 69 years) stroke patients, smokers carrying the Pl(A2) allele were at a higher (OR=5.81, 95% CI=1.26 to 26.80; P=0.024) risk of lacunar infarcts than noncarrier smokers (OR=3.12, 95% CI=1.06 to 9.24; P=0.039). The effect of Pl(A2) and smoking combined on survival was also stronger (OR=8.86, 95% CI=1.68 to 46.55; P=0.010) than the effect of smoking alone (OR=5.06, 95% CI=1.20 to 21.35; P=0.027).

CONCLUSIONS

Our results indicate that prothrombotic genetic factors may interact with smoking by modifying the stroke phenotype and affecting midterm survival.

摘要

背景与目的

吸烟、纤维蛋白原水平升高以及血小板活化均与缺血性卒中风险相关。血小板纤维蛋白原受体糖蛋白（Gp）IIb/IIIa Pl(A1/A2)多态性影响血小板与纤维蛋白原的结合，并提示与吸烟存在相互作用。

方法

我们在卒中、衰老与记忆队列中探讨了吸烟及Pl(A1/A2)多态性与缺血性卒中和生存情况的关联，该队列包括486例连续患者（年龄55至85岁），在缺血性卒中后3个月进行分析，并随访15个月。272例患者可获得由磁共振成像确定的卒中亚型及GpIIb/IIIa Pl(A1/A2)基因型数据。

结果

在多变量分析中，吸烟是与腔隙性梗死风险相关的唯一因素（优势比[OR]=1.87，95%置信区间[CI]=1.05至3.31；P=0.033），并且它也是15个月时死亡（n=24，8.8%）的一个预测因素（OR=5.13，95%CI=1.61至16.36；P=0.006），同时还有年龄（OR=1.10，95%CI=1.01至1.19；P=0.008）。单独的GpIIb/IIIa Pl(A1/A2)多态性与卒中亚型或生存情况无关联。然而，存在吸烟与基因型的联合作用与腔隙性梗死风险（OR=2.10，95%CI=0.90至4.89；P=0.087）以及与生存情况（OR=2.78，95%CI=0.89至8.61；P=0.077）的关联。在较年轻（55至69岁）的卒中患者中，携带Pl(A2)等位基因的吸烟者发生腔隙性梗死的风险（OR=5.81，95%CI=1.26至26.80；P=0.024）高于非携带者吸烟者（OR=3.12，95%CI=1.06至9.24；P=0.039）。Pl(A2)与吸烟联合对生存的影响（OR=8.86，95%CI=1.68至46.55；P=0.010）也强于单独吸烟的影响（OR=5.06，95%CI=1.20至21.35；P=0.027）。