CAJ | 학술논문

目的探讨凝血酶激活的纤溶抑制物(thrombin aetiralable fibrinolysis inhibitor,TAFI)及其编码基因CPB2单核苷酸多态性与冠状动脉粥样硬化性心脏病(冠心病)之间的联系.方法应用聚合酶链反应-限制性片段长度多态性分析技术(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)检测210例冠心病患者和190名正常对照者的TAFI基因编码区Thr325Ile、Tnr147Ala多态性分布特点,同时应用发色底物法和ELISA法分别测定TAFI的活性及抗原,并进一步分析基因多态性与TAFI的活性及抗原之间的关系.结果冠心病组(心肌梗死组及心绞痛组)血浆中TAFI的活性及抗原水平均较对照组显著增高,差异有统计学意义.CPB2基因C1040T(Thr325Ile)及G505A(Thr147Ala)2个位点的3种基因型在冠心病组和对照组的频率分布分别为C1040C(Thr325Thr)67(31.9%)、64(33.6%);C1040T(Thr325Ile)109(51.9%)、92(48.4%);T1040T(Ile325Ile)34(16.2%)、34(17.8%);G505G(Ala147 Ala)75(35.7%)、72(37.8%);G505A(Thr147Ala)112(53.3%)、96(50.5%);A505A(Thr147Thr)23(10.9%)、22(11.7%),经x2检验,基因型分布符合Hardy-Weinberg平衡,并且两组之间各种基因型频率分布差异无统计学意义(P>0.05).在冠心病组和对照组Thr325Ile不同的基因型对TAFI活性没有影响;对TAFI抗原含量的影响则以Thr325Thr纯合基因型者血浆TAFI抗原浓度最高,较其他两型差异有统计学意义(P<0.05),Thr325Ile与TIle325Ile型之间则差异无统计学意义(P>0.05).而Tnr147Ala基因多态性与血浆中TAFI活性及抗原水平之间的差异均无统计学意义(P>0.05).结论 TAFI具有抑制纤溶的作用,可能是冠心病发病的危险因子.TAFI编码区基因Thr325Ile的多态性对血浆中TAFI抗原水平有明显影响,但Thr325Ile、Thr147Ala的多态性与冠心病的发生没有明显的相关性.
목적 탐토응혈매격활적섬용억제물(thrombin aetiralable fibrinolysis inhibitor,TAFI)급기편마기인CPB2단핵감산다태성여관상동맥죽양경화성심장병(관심병)지간적련계.방법 응용취합매련반응-한제성편단장도다태성분석기술(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)검측210례관심병환자화190명정상대조자적TAFI기인편마구Thr325Ile、Tnr147Ala다태성분포특점,동시응용발색저물법화ELISA법분별측정TAFI적활성급항원,병진일보분석기인다태성여TAFI적활성급항원지간적관계.결과 관심병조(심기경사조급심교통조)혈장중TAFI적활성급항원수평균교대조조현저증고,차이유통계학의의.CPB2기인C1040T(Thr325Ile)급G505A(Thr147Ala)2개위점적3충기인형재관심병조화대조조적빈솔분포분별위C1040C(Thr325Thr)67(31.9%)、64(33.6%);C1040T(Thr325Ile)109(51.9%)、92(48.4%);T1040T(Ile325Ile)34(16.2%)、34(17.8%);G505G(Ala147 Ala)75(35.7%)、72(37.8%);G505A(Thr147Ala)112(53.3%)、96(50.5%);A505A(Thr147Thr)23(10.9%)、22(11.7%),경x2검험,기인형분포부합Hardy-Weinberg평형,병차량조지간각충기인형빈솔분포차이무통계학의의(P>0.05).재관심병조화대조조Thr325Ile불동적기인형대TAFI활성몰유영향;대TAFI항원함량적영향칙이Thr325Thr순합기인형자혈장TAFI항원농도최고,교기타량형차이유통계학의의(P<0.05),Thr325Ile여TIle325Ile형지간칙차이무통계학의의(P>0.05).이Tnr147Ala기인다태성여혈장중TAFI활성급항원수평지간적차이균무통계학의의(P>0.05).결론 TAFI구유억제섬용적작용,가능시관심병발병적위험인자.TAFI편마구기인Thr325Ile적다태성대혈장중TAFI항원수평유명현영향,단Thr325Ile、Thr147Ala적다태성여관심병적발생몰유명현적상관성.
Objective To investigate the association of thrombin activatable fibrinolysis inhibitor(TAFI)and its encoding gene CPB2 polymorphism in patients with coronary heart disease(CHD).Methods The CPB2 gene polymor-phisms of Thr325Ile and Thr147Ala were analyzed with polymerase chain reaction-restriction fragment length polymor-phism(PCR-RFLP)in patients of acute myocardial infarction(n=1130),acute angina pectoris (n=110)and a control group(n=190).The antigen(Ag)and activity(Act)of the TAFI were determined by sandwich enzynle link immunosor-hent assay specific for human TAFI and chromogenic assay for activated human TAFI in plasma,respectively,The rela-tionship between Thr325Ile and Thr147Ala gene polymorphism and TAFI Ag and Act were also analyzed.Results Plas-ma TAFI Act and TAFI Ag in acute myocardial infarction group and acute angina pectoris group(CHD patients group) were both significantly higher than those of the control group.The genotype frequencies of Thr325Ile(C1040T)and Thr147Ala(G505A)were as the following:C1040C(Thr325Thr)67(31.9%)and 64(33.6%);C1040T(Thr325Ile) 109(51.9%)and 92(48.4%);T1040T(Ile325Ile)34(16.2%)and 34(17.8%);G505G(Ala147 Ala)75(35.7%) and72(37.8%);G505A(Thr147Ala)112(53.3%)and 96(50.5%);A505A(Thr147Thr)23(10.9%)and 22 (11.7%),in the CHD patients and control respectively.x2 analysis showed no significant difference in the Thr325Ile and Thr147Ala polymorphism distributiom(P>0.05).In addition,at the 325 position,the TAFI antigen of the Thr325Thr was higher than that of the other genotypes(Thr325Ile and Ile325Ile,P<0.05).There was no statistical significance between the TAFI antigen of the Thr32511e and lle325Ile (P>0.05). No significant correlation was found between the TAFI Act and the Thr325Ile polymorphism. At the position 147, significant correlation between the polymor-phism of the Thr147Ala and TAFI Ag and Act was not found. Conclusion TAFI plays an important role in anti-fibfinol-ysis. It might be a risk factor for acute myocardial infarction and acute angina poctoris. The Thr325Ile polymorphism had obvious effect on TAFI antigen levels,but the Thr325Ile and Thr147Ala polymorphism had no association with coronary heart disease.