β-纤维蛋白原-455 G/A基因多态性对缺血性脑卒中患者血浆纤维蛋白原水平的影响

Effect of β-Fibrinogen-455 Gene Polymorphism on Plasma Fibrinogen Levels in Patients with Ischemic Stroke

为了分析 β 纤维蛋白原 4 5 5G A(β Fg 4 5 5G A)基因多态性与环境因素对血浆Fg水平及缺血性脑卒中发病的影响 ,应用聚合酶链反应 (PCR)及限制性内切酶分析的方法 ,分析了 10 4例缺血性脑卒中患者及 15 6例健康人的 β Fg 4 5 5G A基因多态现象 ,用比浊法测定血浆Fg水平。研究结果显示 ,病例组血浆Fg水平明显高于对照组 (P <0 .0 1)。无论男、女患者与对照相比 ,A等位基因携带者血浆Fg水平均比同组GG基因型者明显升高 (P <0 .0 5 )。对照组内只有A等位基因携带者随年龄增长血浆Fg水平有明显升高 (P <0 .0 5 )。病例组男性按吸烟及基因型情况分组 ,在GA基因型中 ,吸烟组血浆Fg水平高于不吸烟与戒烟组 (P <0 .0 5 ) ;GG基因型组吸烟与否对Fg水平无显著影响 (P >0 .0 5 )。病例组与对照组A等位基因频率分布无差异。结论提示 ,A等位基因携带者血浆Fg水平升高 ,并随年龄、吸烟而更加显著 ,提示 β Fg 4 5 5A等位基因携带者血浆Fg水平更易受环境因素影响而升高 ,故此基因多态性可用于易感人群的检测 。

In large prospective studies, plasma fibrinogen levels have been shown to be an independent risk factor of vascular disease, including ischemic stroke. Elevated plasma fibrinogen in an individual could be due to the presence of predisposing genetic and/or environmental factors, such as smoking. Of the polymorphisms studies to date, the β fibrinogen 455 (β Fg 455) G→A substitution in the 5′ flanking region is associated with the most consistent difference in plasma fibrinogen levels in both case control studies and in selected groups of healthy individuals. In order to further elucidate the role of the β Fg 455 G→A substitution in determining fibrinogen levels and susceptibility to ischemic stroke in case control population, including 104 individuals with verified ischemic stroke and 156 healthy individuals. Turbidimetriy assays were used to measure plasma fibrinogen levels of all samples. The β Fg 455 G→A mutation was identified by the polymerase chain reaction followed by restriction enzyme digestion of the amplified DNA with HaeⅢ. The plasma fibrinogen level in patients with ischemic stroke 〔(3.51±1.09) g/L〕 was significantly higher than that in the control 〔(3.08±0.71) g/L〕 (P<0.01). The A allele is associated with elevated fibrinogen levels in both patients and controls. The plasma fibrinogen levels in controls with A allele in elder people were higher than in younger people (P<0.05). Those with A allele in males of ischemic stroke had significantly higher plasma fibrinogen levels in smokers than in non smokers and ex smokers (P<0.05), but it was not significantly difference in subjects of GG genotype (P> 0.05). Our data demonstrates an association of the β Fg promoter A 455 allele with higher fibrinogen levels in the general population, and suggests that the A allele may be a susceptible predictor of ischemic stroke, particularly in aging and smoking.