纤维蛋白原基因多态性与缺血性心脑血管病的关系

目的：调查健康人、心肌梗死患者及脑梗死患者的纤维蛋白原（Fg)β-455G/A、-148C/T、448G/A基因多态性频率分布、Fg分子反应性及与血浆Fg水平的关系。方法：用限制性片段长度多态性分析基因频率分布，用计算机辅助的纤维蛋白单体聚合反应分析方法和Clauss法分析血浆Fg水平。结果：等位基因－455A、－148T和448A在正常人中的频率分别是0．185，0．194及0．192；在心肌梗死患者中的频率分别是0．295，0．318及0．307；在脑梗死患者中的频率分别是0．177，0．193及0．182。心肌梗死患者中－455A、－148T和448A的频率比健康人明显升高。3个多态性位点－455G、－148C和448G或－455A、－148T和448A分别紧密连锁，符合率超过98％。心脑血管病患者的Fg功能明显增高且与Fg水平相关。3个多态性位点不同基因型组血浆Fg水平差异无显著性。结论：3对等位基因紧密连锁不平衡，不同基因型组血浆Fg水平差异无显著性，心肌梗死患者中－455A、－148T和448A的频率比健康人明显升高。提示Fgβ-455G/A、-148C/T和448G／A三种基因多态性与血浆Fg水平无关，而与心肌梗死的发病相关。心脑血管病患者不仅Fg功能明显增高，且与Fg水平相关。

The relationship of beta-fibrinogen gene polymorphisms and ischaemic cardiocerebral vascular disease

OBJECTIVE: To analyze the frequency of beta-fibrinogen (beta-Fg) gene -455G/A, -148C/T and 448G/A polymorphism, fibrinogen molecular reactivity and their association with plasma fibrinogen levels in health adults, myocardial infarction and cerebral infarction disease. METHODS: The beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms were analyzed by restriction fragment length polymorphism (RFLP). Fibrinogen molecular reactivity was analyzed for the conversion kinetics of fibrinogen into fibrin by a computer assistant procedure. Plasma fibrinogen levels were determined by Clauss method. RESULTS: The frequencies of -455A, -148T, 448A allele in health adults were 0.185, 0.194 and 0.192, in myocardial infarction disease 0.295, 0.318 and 0.307, in cerebral infarction disease 0.177, 0.193 and 0.182, respectively. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. There were close linkage between -455G, -148C and 448G or -455A, -148T and 448A, the correspondence was over 98%. There are no differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level. CONCLUSION: The three polymorphisms loci are strong linkage disequilibrium. There are no significant differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. It suggest that there was no association between beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms and plasma fibrinogen levels, but did in myocardial infarction disease. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level.