纤维蛋白原Bβ多位点基因多态性与其功能表达和脑梗死类型的关系

The relationship of multi-locus gene polymorphisms,functional expression of fibrinogen Bβ-chain and the type of cerebral infarction

目的:研究人体纤维蛋白原(Fibrinogen,Fg)Bβ-854G/A、-455G/A、-249C/T、-148C/T、448G/A和Bcl-1G/A的基因多态性与血浆Fg浓度、分子聚合活性等功能表达指标和脑梗死类型的关系。方法:采用病例对照研究,选取2002年7月-2003年6月在开滦医院神经内科住院的急性脑梗死患者160例,其中脑动脉主干支梗死组(MCI)54例、脑动脉穿通支梗死组(PCI)106例,选取同期在开滦医院健康查体且结果均正常的志愿者160例为对照组,测定所有样本的血浆Fg浓度、纤维蛋白单体聚合反应速率(FMPV)、最大吸光度(Amax)及其比值(FMPV/Amax)等反映Fg分子聚合功能参数和甘油三酯(TG)、极低密度脂蛋白(VLDL)等血液生化指标,应用聚合酶链反应-限制性内切酶片段长度多态性技术进行FgBβ链六位点的基因多态性检测。结果:MCI组Fg浓度、FMPV、FMPV/Amax及PCI组TG、VLDL、FMPV均高于对照组(P<0.05);FgBβ-854 A和Bcl-1 A等位基因在三组间分布频率有统计学差异,且MCI和PCI组的GA、AA型分布频率高于对照组(P<0.05),其余位点等位基因及基因型分布在三组间均无显著性差异(P>0.05);MCI组FgBβ-249T携带者人群Fg、FMPV低于CC型(P<0.05);PCI组-148T携带者人群FMPV/Amax高于CC型(P<0.05);对照组Bcl-1A携带者人群Fg浓度高于GG型(P<0.05),而PCI组此人群则FMPV高于GG型(P<0.05)。结论:FgBβ链5’端启动子区-249多态性位点可影响血浆FMPV功能的表达,-148位点是调控血浆Fg分子聚合功能表达的重要部位;3’端Bcl-1是血浆Fg浓度的重要基因调控位点,其变异基因型人群是MCI的遗传易感人群;血浆Fg浓度、FMPV/Amax和FMPV同时异常是MCI的重要危险因素,而仅FMPV和TG异常则易发PCI。

Objective：To study the correlation of β-fibrinogen-854G/A,-455G/A,-249C/T,-148C/T,448G/A and Bcl-1G/A polymorphisms,functional expression of plasma fibrinogen concentration,molecular reactivity,and the type of cerebral infarction.Methods：A case-control study was used to analyze 54 patients with main-trunk cerebral infarction（MCI）,106 patients with penetrating-arterial cerebral infarction（PCI） and 160 healthy cases as control group in Kailuan Hospital between July 2002 and June 2003.Gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）.Fg concentration,fibrin monomer polymerized velocity（FMPV）,absorbance maximum（Amax）,FMPV/Amax and biochemistry factors including TG were measured.Results：Fg concentration,FMPV,FMPV/Amax in the MCI group and TG,VLDL and FMPV in the PCI group were higher than in the control group（P〈0.05）.The frequencies of-854A and Bcl-1A alleles had significant difference among three groups,and the frequencies of GA and AA genotypes in the MCI and PCI groups were higher than in the control group（P〈0.05）,however,no different genotypes and allele frequencies of the remaining sites were found in the three groups（P〉0.05）.Fg concentration and FMPV of allele T carriers in the MCI group were less than that of-249C/C homozygous ones（P〈0.05）;FMPV/Amax of allele T carriers in the PCI group was higher than that of-148C/C homozygous ones（P〈0.05）;with allele A carriers,Fg concentration of control group and FMPV of PCI group were higher than that of Bcl-1 wild homozygote（P〈0.05）.Conclusion：Bβ-249 C/T polymorphism in the 5-flanking promoter region can influence the expression of plasma FMPV,Bβ-148 locus is the main regulation location of Fg molecular conglomerate function.Bcl-1 locus in the 3-flanking region is an important gene regulator of plasma Fg concentration,moreover,people with its mutated genotypes are susceptible to MCI.The abnormal plasma Fg concentration,FMPV/Amax and FMPV simultaneously are important risk factors for MCI,and only abnormal FMPV and TG are prone to PCI.