β-纤维蛋白原基因-455G/A多态性与血浆纤维蛋白原水平及腔隙性脑梗死的相关性

Correlation betweenβ-fibrinogen gene-455G/A polymorphism and plasma fibrinogen level and lacunar infarction

目的探讨β-纤维蛋白原(β-fibrinogen,FGB)基因-455G/A多态性与血浆纤维蛋白原(fibrinogen,Fg)水平及腔隙性脑梗死(lacunar infarction,LI)的相关性。方法前瞻性连续纳入2018年6月至2019年8月期间在辽宁省人民医院神经内科住院的无脑血管病和痴呆的受试者。根据颅脑MRI检查有无LI及脑白质高信号(white matter hyperintensities,WMHs),将患者分为LI组、LI+WMHs组及对照组。应用聚合酶链反应及基因测序技术检测FGB-455G/A位点多态性,采用比浊法测定血浆Fg水平。应用多变量logistic回归分析确定LI及LI+WMHs的独立危险因素。结果共纳入202例受试者,其中LI组48例,LI+WMHs组58例,对照组96例。LI组和LI+WMHs组高血压、血脂异常和高同型半胱氨酸血症的患者构成比以及血浆Fg水平均显著高于对照组(P均<0.05)。3组间FGB-455G/A基因型和等位基因频率差异均无统计学意义。AG+AA基因型者血浆Fg水平显著高于GG基因型者(P<0.001),而人口统计学和其他血管危险因素均无显著差异。各基因型受试者血浆Fg水平由高至低均依次为LI+WMHs组、LI组、对照组,且两两比较差异均具有统计学意义(P<0.05)。多变量logistic回归分析表明,高血压[优势比(odds ratio,OR)2.289,95%可信区间(confidence interval,CI)1.015~5.166,P=0.046;OR 2.457,95%CI 1.021~5.913,P=0.045]、血脂异常(OR 2.681,95%CI 1.217~5.905,P=0.014;OR 3.061,95%CI 1.296~7.233,P=0.011)及血浆Fg水平(OR 5.038,95%CI 2.328~10.902,P<0.001;OR 20.198,95%CI 8.143~50.097,P<0.001)均为LI和LI+WMHs的独立危险因素。结论血浆Fg水平升高、血脂异常及高血压是LI和LI+WMHs的独立危险因素。虽然FGB-455G/A多态性可影响血浆Fg水平,但其与LI和LI+WMHs均无显著相关性。

Objective To investigate the correlation betweenβ-fibrinogen(FGB)gene-455G/A polymorphism and plasma fibrinogen(Fg)level and lacunar infarction(LI).Methods From June 2018 to August 2019,consecutive subjects without cerebrovascular disease and dementia admitted to the Department of Neurology,the People's Hospital of Liaoning Province were enrolled prospectively.According to whether there was LI or white matter hyperintensities(WMHs)in brain MRI,the patients were divided into LI group,LI+WMHs group and control group.Polymerase chain reaction and gene sequencing technology were used to detect FGB-455G/A polymorphism.The turbidimetry was used to measure plasma Fg level.Multivariate logistic regression analysis was used to determine the independent risk factors for LI and LI+WMHs.Results A total of 202 subjects were included,including 48 in the LI group,58 in the LI+WMHs group,and 96 in the control group.The proportions of patients with hypertension,dyslipidemia,and hyperhomocysteinemia and plasma Fg levels in the LI and LI+WMHs groups were significantly higher than those in the control group(all P<0.05).There was no statistical difference in FGB-455G/A genotype and allele frequency between the three groups.The plasma Fg level of AG+AA genotype was significantly higher than that of GG genotype(P<0.001),and there was no significant difference in demography and other vascular risk factors.Regardless of the genotype,the plasma Fg level was highest in the LI+WMHs group,followed by the LI group and the control group,and the differences between each pair were statistically significant(P<0.05).Multivariate logistic regression analysis showed that hypertension(odds ratio[OR]2.289,95%confidence interval[CI]1.015-5.166,P=0.046;OR 2.457,95%CI 1.021-5.913,P=0.045),dyslipidemia(OR 2.681,95%CI 1.217-5.905,P=0.014;OR 3.061,95%CI 1.296-7.233,P=0.011)and plasma Fg levels(OR 5.038,95%CI 2.328-10.902,P<0.001;OR 20.198,95%CI 8.143-50.097,P<0.001)were all the independent risk factors for LI and LI+WMHs.Conclusions The increased plasma Fg level,dyslipidemia,and hypertension were the independent risk factors for LI and LI+WMHs.Although FGB-455G/A polymorphism could affect plasma Fg level,it had no significant correlation with LI and LI+WMHs.