纤维蛋白原Bβ链七个位点基因单体型与脑梗死的关系

Relationship of haplotypes of seven polymorphisms in FibBβ-chain with cerebral infarction

目的研究纤雏蛋白原（Fib）Bβ-1420G／A、-993C／T、1689T／G、BsmAIG，／C、161／D、345C／T、HinfIA／c位点基因多态性及其构建的单体型与血浆Fib功能表达及脑梗死的关系。方法选择首次急性脑梗死患者90例（脑梗死组），健康体检者859例（对照组），填写临床调查量表，测定血液生化指标和血浆Fib浓度、纤维蛋白单体聚合反应速率（FMPV）、FMPV／最大吸光度（Amax）等指标，同时检测FibBβ链7个位点的基因型，并筛选其常见单体型行相关性分析。结果脑梗死组FibBβ链7个基因多态性位点中仅Bβ-1420AA基因型频率明显高于对照纽，差异有统计学意义（p〈0．01），H1、H2、H3、H4、H5、H6、H7常见单体型在2组的频率分布差异有统计学意义（X2=110．47，P〈0．01）。以脑梗死为因变量回归分析，筛选出FMPV、FMPV／Amax、FibHinfI、H2、H4、H6；以FMPV为因变量，筛选出收缩压、血糖、16I／D位点；以Amax为因变量，筛选出H5单体型；以FMPV／Amax为因变量，筛选出脑梗死、饮酒史、Fib-1420c／A（P〈0．05）。结论FMPV和BIa-1420变异纯合子及HinfI变异基因型是发生脑梗死的重要危险因素；FibBβ链基因多态性位点及其各种单体型在脑梗死发病中并非仅通过影响血浆Fib功能表达而发挥作用。

Objective To investigate the impact of FibBβ-1420G/A,-993C/T,1689T/G,BsmAIG/ C, I6I/D, 345C/T, HinfIA/C polymorphisms and their haplotypes on functional expression of plasma fibrinogen and the relationship of them with cerebral infarction（CI）. Methods 859 healthy subjects from Kailuan Group and 90 patients with the first cerebral infarction were enrolled in this study. Blood biochemistry, fibrinogen concentration, fibrin-monomer polymerized velocity （FMPV）, absorbance maximum（Amax） and FMPV/A were measured. The seven polymorphisms were detected,and common haplotypes were selected to analyze their correlation with CI. Results Only -1420AA genotype frequency of seven loci between CI and control group had significant difference （P〈0.01）;the distribution frequecies were statistically significantly different in their common haplotypes of H1,H2,H3,H4,HS,H6 and H7 between the two groups（X2=110. 47,P〈0.01）. In logistic regression analysis of correlative factors to cerebral infarction, FMPV, FMPV/A HinfI allele, H2 haplotype, H4 haplotype, and H6 haplotypes were selected, respectively （P〈0.05） ;the result of multiple stepwise regression analysis showed that using FMPV as dependent variable,SBP,Glu,and I6I/D were selected; using Amax as dependent variable, H5 haplotype was screened out;using FMPV/Amax as dependent variable, CI, drinking,-1420G/A genotype were se- lected in turn （P〈0.05）. Conclusion FMPV, Bβ-1420 variant homozygote and HinfI mutant genetype are important risk factors of CI. Gene polymorphism and their haplotypes of FibBβ have important effect on the pathogenetis of CI, by no means only through influncing plasma Fib functional expression,and its mechanism will be further studied.