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  

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

作　　者：孙川[1] 梁亮[1] 李巍景[2] 肖锋[1] 苏雨江[3] 姚震[2] 陈晓丹[4] 邢波[3] 陈莫水[3] 刘国勋[5] 蔡望伟[1] 

机构地区：[1]海南医学院生物化学教研室,海南省海口市571101 [2]海南医学院附属医院心内科,海南省海口市570102 [3]海口市人民医院心内科,海口市570208 [4]海南医学院附属医院检验科,海南省海口市570102 [5]广东医学院附属医院血液研究室,广东省湛江市524001

出　　处：《中国动脉硬化杂志》2007年第9期699-702,共4页Chinese Journal of Arteriosclerosis

基　　金：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)

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。Aim To investigate the polymorphisms and haplotypes in α-fibrinogen and β-brinogen gene and their relationship to coronary heart disease （CHD）. Methods Plasma fibrinogen level was measured by turbidmetrie assay. The TaqI polymorphism in α-fibrinogen gene and the single nucleotide polymorplusms - 455G/A, - 249C/T, - 148C/T, ＋ 1689T/G, BsmAIG/C, 448G/A, BcllG/A and HinflA/C in β-fibrinogen gene were characterized by PCR-RFLP in one hundred and twenty one cases of CHD and one hundred and thirty healtlry individuals from Hainan Han population. Haplotypes were estimated by the EH ＋ program. The statistical differences of allelic, genotype and haplotype frequuencies between the case group and the control were estimated by Chi square test. Results The allelic frequencies of the polymorplfisms - 455A, - 148T, 448A wet＇e 0.343, 0.351 and 0.326 in CHD group, whereas the allellc fi＇equencies of the polymorphisms -455A, - 148T, 448A were 0.254, 0. 254 and 0.242 in the control. The allelic fi＇ecptencles of - 455A, - 148T, 448A were higher in the CHD group than in the control （ P 〈 0.05 ）. The allelie frequencies of the other six polymorphisms were not significantly different between theCHD group and tile control （P 〉 0.05）. The odds ratios （OR） with the rare alleles of A^-455,T^-148 and A^448 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, [3- 148C, β＋ 1689T, βBsmAI G, 13448G, βBcll G, βHinfI A and αTaqI T2 were lower in the CHD group than in the control. Among the haplotypes constructed from polymorplisms including - 455G/A, - 249C/T, - 148C/T in the pro- moter region of β-fibrinogen gene, haplotype hl with - 455G, - 249C and - 148 C alleles appeared more frequently in control group （ P 〈 0.01 ）, whereas haplotype 14 with - 455A, - 249C and - 148C and haplotype h6 with - 455A, - 249C and -148T occurred more frequently in the CHD group （ P 〈 0.01 ）. Conclusins The res

关 键 词：分子生物学 纤维蛋白原 核苷酸多态性 冠心病 单体型 

分 类 号：Q7[生物学—分子生物学]