[海南汉族人群中与缺血性脑卒中相关的α、β纤维蛋白原基因单倍型及核苷酸多态性的相关性分析]

[A related analysis for alpha, beta fibrinogen gene haplotypes and nucleotide polymorphisms associated with the ischemic stroke in Hainan Han population].

作者信息

Liang Liang, Sun Chuan, Liao Xiao-ping, Xiao Feng, Chen Xiao-dan, Huang Shi-xiong, Tang Xiao-lan, Wen Guo-qiang, Long Zhi-gang, Wang Xiao-ying, Liu Guo-xun, Cheng Shuang, Cai Wang-wei

机构信息

Department of Biochemistry, Hainan Medical College, Haikou, Hainan, 571101 PR China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006 Jun;23(3):316-9.

PMID:16767673

Abstract

OBJECTIVE

To analyze the association of that the polymorphisms and haplotypes of Taq I site in beta fibrinogen gene and the single nucleotide sites -455 G/A, -249 C/T, -148 C/T, +1689T/G, Bsm A I G/C, 448 G/A, Bcl I G/A, Hinf I A/C in beta-fibrinogen gene are linked up with the ischemic stroke(IS).

METHODS

Turbidmetric assay was used to measure the plasma fibrinogen level of one hundred and sixty cases with ischemic stroke and one hundred and thirty healthy individuals from Hainanese Han population. The polymorphisms and genotypes were characterized by PCR-RFLP. Hardy-Weinberg equilibrium and statistical differences of allelic, genotype and haplotype frequencies were obtained by Chi-square test. Pairwise linkage disequilibrium was calculated and haplotypes of nine or four polymorphisms were estimated by the EH + program.

RESULTS

There were highly significant differences in genotype frequencies and allelic frequencies of the polymorphisms -455 G/A, -148 C/T, 448 G/A, which happened between the IS group and control subjects (P< 0.01). However, the significant differences of the allelic frequencies in the other six polymorphisms were not found between the IS group and the control (P> 0.05). The odds ratio(OR) with the rare alleles of A -455, T -148 and A 448 is 2.46, 2.30 and 2.08 (95% confidence interval 1.153%-3.924%, 1.429%-3.694% and 1.298%-3.329%) respectively. No definite haplotype block was found by linkage disequilibrium analysis in the control group and the IS group. Association of haplotypes constructed from the nine polymorphisms with IS was not found. Among the haplotypes constructed from four polymorphisms including -455 G/A, -148 C/T, 448 G/A alleles, haplotype differences were found between the control group and the IS group. Haplotypes with G -455, C -148, G448 alleles appeared more frequently in control group(P< or = 0.01), whereas haplotypes with A -455, T -148, A 448 occurred more frequently in the IS group(P< 0.01).

CONCLUSION

The results of multi-allele and haplotype analysis indicated that the polymorphisms -455 G/A, -148 C/T, 448 G/A in beta fibrinogen gene were the possible risk factors associated with the occurrence of ischemic stroke in Hainan Han population.

摘要

目的

分析β纤维蛋白原基因Taq I位点的多态性和单倍型以及β纤维蛋白原基因中-455 G/A、-249 C/T、-148 C/T、+1689T/G、Bsm A I G/C、448 G/A、Bcl I G/A、Hinf I A/C单核苷酸位点与缺血性脑卒中（IS）的相关性。

方法

采用比浊法测定160例缺血性脑卒中患者和130名海南汉族健康个体的血浆纤维蛋白原水平。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对多态性和基因型进行鉴定。采用卡方检验获得Hardy-Weinberg平衡以及等位基因、基因型和单倍型频率的统计学差异。计算成对连锁不平衡，并通过EH +程序估计9个或4个多态性的单倍型。

结果

-455 G/A、-148 C/T、448 G/A多态性的基因型频率和等位基因频率在IS组和对照组之间存在高度显著差异（P<0.01）。然而，IS组和对照组之间在其他6个多态性的等位基因频率上未发现显著差异（P>0.05）。-455 A、-148 T和448 A稀有等位基因的比值比（OR）分别为2.46、2.30和2.08（95%置信区间分别为1.153%-3.924%、1.429%-3.694%和1.298%-3.329%）。在对照组和IS组中，通过连锁不平衡分析未发现明确的单倍型块。未发现由9个多态性构建的单倍型与IS的相关性。在由包括-455 G/A、-148 C/T、448 G/A等位基因的4个多态性构建的单倍型中，对照组和IS组之间存在单倍型差异。-455 G、-148 C、448 G等位基因的单倍型在对照组中出现频率更高（P≤0.01），而-455 A、-148 T、448 A单倍型在IS组中出现频率更高（P<0.01）。