纤维蛋白原Bβ-455G/A、-854G/A基因多态性和功能表达与脑梗死的关系

The relationship between β-fibrinogen gene -455G/A,-854G/A polymorphisms,plasma fibrinogen concentration and molecular reactivity on cerebral infarction

目的:探讨血浆纤维蛋白原(Fg)Bβ-455G/A、-854G/A基因多态性和Fg浓度、分子活性等功能表达与脑梗死(CI)的关系。方法:采用病例对照研究方法,选取160例首发急性CI患者、114例陈旧CI患者及162例正常对照者;应用聚合酶链反应-限制性酶切法(PCR-RFLP)进行基因多态性分析;并测定血浆Fg浓度、Fg单体聚合反应速率(FMPV)、最大光密度(A-max)、FMPV/Amax等参数及血糖等5项生化指标。结果:Bβ-455等位基因和基因型分布频率在三组间无统计学差异(P>0.05);Bβ-854等位基因A在急性CI组分布频率明显高于正常组(P<0.01),其变异型分布频率高于正常组(P<0.05);FMPV在急性CI组和陈旧CI组明显高于正常组(P<0.01),FMPV/Amax、Fg浓度在陈旧CI组高于正常组(P<0.01,P<0.05);三组中Fg浓度、FMPV、Amax及FMPV/Amax与Bβ-455基因型无相关性;陈旧CI中Bβ-854变异型组Fg浓度、FMPV及Amax明显高于野生型组(P<0.01);以Fg浓度、FMPV、Amax为因变量的多元逐步回归分析均筛选出Bβ-854基因型。结论:FgBβ-455基因多态性对血浆Fg浓度和分子聚合活性的表达没有明显的影响,Bβ-854位点基因多态性可能参与调控血浆Fg浓度和血浆纤维蛋白单体总体聚合功能的表达,但对血浆Fg分子聚合活性表达没有明显的影响,且Bβ-854变异型人群可能是脑梗死疾病的遗传易感人群,有脑梗死病史患者的血浆Fg浓度和分子聚合功能增高程度可能比急性期患者更严重。

Objective：To study the relationship among linkage of Bβ-455G/A, -854G/A polymorphisms, plasma fibrinogen concentration and molecular reactivity in cerebral infarction. Methods： A case-control study was used to analyze 160 patients with acute cerebral infarction, 114 patients with remote cerebral infarction and 162 healthy individuals; Bβ-455G/A,-854G/A polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）; F g concentration, fibrin monomer polymerized velocity（FMPV）, absorbance maximum（Amax）, FMPV/Amax and five biochemistry factors including glucose were measured. Results： No different genotypes and allele frequencies of Bβ-455G/A was found in the three groups（ P 〉 0.05） ; A-854 in the acute cerebral infarction group was significantly higher than in the normal group（ P 〈 0.01）, and its mutated genotype frequency was higher than in the normal group（ P 〈 0.05） ; FMPV in both acute and remote cerebral infarction group was significantly higher than in the normal group（ P 〈 0.01 ）. In the remote cerebral infarction group FMPV/Amax was significantly higher and Fg concentration was higher than in the normal group（ P 〈 0.01, P 〈 0.05） ; Bβ-455 genotypes had no impact on Fg concentration, FMPV, Amax and FMPV/Amax in the three groups; Only Fg concentration, FMPV and Amax in the remote cerebral infarction group with mutated genotype of Bβ-854 were significantly higher than with wild genotype（ P 〈 0.01 ） ; Fg concentration, FMPV and Amax as the dependent variable, Bβ-854 gene was selected by multiple regression analysis. Conclusion： There is no correlation between Bβ-455 and Fg concentration, molecular reactivity. A-854 and mutated genotype of Bβ-854 may have impact on Fg concentration and FMPV except FMPV/Amax, and the genotype may also be related in cerebral infarction. Furthermore, Fg concentration and molecular reactivity in the remote cerebral infarction may be higher than in the acute cerebral infarction.