α和β纤维蛋白原基因核苷酸多态性及其单体型与冠心病的关系
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国家自然科学基金(30060037);;教育部科学技术研究重点项目(03147);;海南医学院重点学科项目(2005-1)


Nucleotide Polymorphisms and Haplotypes in α-and β-Fibrinogen Genes and Their Relationship to Coronary Heart Disease
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    摘要:

    目的研究α纤维蛋白原基因TaqI多态性和β纤维蛋白原基因-455G/A-、249C/T、-148C/T、+1689T/G、448G/A、BsmAI、BclIG/A、HinfIA/C单核苷酸多态性及其单体型与冠心病的关系。方法采用聚合酶链反应限制片长多态性法确定基因型,采用比浊法测定血浆纤维蛋白原水平,采用EH+程序分析核苷酸多态性的单体型,采用卡方检验分析病例组和对照组的等位基因频率、基因型频率及单体型频率的差异。结果β纤维蛋白原基因-455A、-148T和448A的等位基因频率在冠心病组分别为0.343、0.351和0.326,在对照组分别为0.254、0.254和0.242,冠心病组β纤维蛋白原基因-455A、-148T和448A的等位基因频率明显高于对照组(p<0.05),β纤维蛋白原基因-455A、-148T和448A携带者患冠心病的相对危险度比非携带者分别大1.53倍、1.59倍和1.51倍;其他位点的等位基因频率在两组间无统计学差异。β纤维蛋白原基因-455G、-249C、-148C、+1689T、448G、BclIG、HinfIA和a纤维蛋白基因TaqI T2位点构成的单体型H16在病例组中的频率比对照组低(p<0.05)。以启动子区3个位点构建的单体型中,由-455G、-249C和-148C构成的单体型h1在病例组中的频率低于对照组(p<0.01),由-455A、-249C、-148C构成的单体型h5和由-455A、-249C、-148T构成的单体型h6在病例组中的频率高于对照组(p<0.05和p<0.01)。结论β纤维蛋白原基因-455G/A、-148C/T和448G/A单核苷酸多态性与冠心病关联,β纤维蛋白原基因-455A、-148T和448A可能是与冠心病相关的遗传危险因素。

    Abstract:

    Aim To investigate the polymorphisms and haplotypes in α-fibrinogen and β-fibrinogen gene and their relationship to coronary heart disease(CHD). Methods Plasma fibrinogen level was measured by turbidmetric assay. The TaqI polymorphism in α-fibrinogen gene and the single nucleotide polymorphisms-455G/A,-249C/T,-148C/T,+1689T/G,BsmAIG/C,448G/A,BclIG/A and HinfIA/C in β-fibrinogen gene were characterized by PCR-RFLP in one hundred and twenty one cases of CHD and one hundred and thirty healthy individuals from Hainan Han population.Haplotypes were estimated by the EH+program.The statistical differences of allelic,genotype and haplotype frequencies between the case group and the control were estimated by Chi square test. Results The allelic frequencies of the polymorphisms-455A,-148T,448A were 0.343,0.351 and 0.326 in CHD group,whereas the allelic frequencies of the polymorphisms-455A,-148T,448A were 0.254,0.254 and 0.242 in the control.The allelic frequencies of-455A,-148T,448A were higher in the CHD group than in the control(p<0.05).The allelic frequencies of the other six polymorphisms were not significantly different between the CHD group and the control(p>0.05).The odds ratios(OR) with the rare alleles of A-455 、T-148 and A448 were 1.53,1.59 and 1.51 respectively.Haplotypes constructed from the nine polymorphisms showed that the frequency haplotype H16 with β-455G,β-249C,β-148C,β+1689T,βBsmAI G,β448G,βBclI G,βHinfI A and αTaqI T2 were lower in the CHD group than in the control.Among the haplotypes constructed from polymorphisms including-455G/A,-249C/T,-148C/T in the promoter region of β-fibrinogen gene,haplotype h1 with-455G,-249C and-148 C alleles appeared more frequently in control group(p<0.01),whereas haplotype h5 with-455A,-249C and-148C and haplotype h6 with-455A,-249C and-148T occurred more frequently in the CHD group(p<0.01). Conclusions The results of multi-allele and haplotype analysis indicated that the polymorphisms-455G/A,-148 C/T and 448G/A in beta fibrinogen gene were associated with CHD in Hainan Han population.The allele with-455A,-148 T and 448 A may represents a genetic risk factor for CHD.

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孙川,梁亮,李巍景,肖锋,苏雨江,姚震,陈晓丹,邢波,陈莫水,刘国勋,蔡望伟.α和β纤维蛋白原基因核苷酸多态性及其单体型与冠心病的关系[J].中国动脉硬化杂志,2007,15(9):699~702.

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  • 收稿日期:2007-02-08
  • 最后修改日期:2007-08-01
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