cyp2c19基因多态性、高水平FIB对氯吡格雷抗凝效应的相关性研究

Study on correlation between cyp2c19 gene polymorphisms and high concentration of fibrinogen with clopidogrel resistance

目的研究冠心病患者中cyp2c19基因多态性、高水平纤维蛋白原（FIB）与氯吡格雷抗凝效应的关系。方法选取2015年5-11月正在服用氯吡格雷的冠心病患者611例,并对其cyp2c19基因特征和FIB水平进行分析。将患者分为cyp2c19基因纯合子强代谢型组（n=261）、杂合子强代谢型组（n=272）及弱代谢型组（n=78）;611例冠心病患者中有408例患者检测凝血项,分为高水平FIB组（n=116）、正常水平FIB组（n=224）及低水平FIB组（n=68）;再分为cyp2c19基因弱代谢型且高水平FIB组（n=24）、cyp2c19基因纯合子强代谢型且高水平FIB组（n=48）,cyp2c19基因杂合子强代谢型且高水平FIB组（n=44）,比较3组的凝血酶时间（TT）。结果 cyp2c19基因型别有＊1/＊1、＊1/＊2、＊1/＊3、＊2/＊2、＊2/＊3、＊3/＊3。经基因芯片检测发现,上述各型分别为261例（占42.7%）、235例（占38.4%）、37例（占6.0%）、60例（占9.8%）、17例（占2.9%）、1例（占0.2%）。cyp2c19＊1、＊2和＊3等位基因频率分别为65.0%（794/1 222）、30.5%（373/1 222）和4.5%（55/1 222）;纯合子强代谢型组占42.7%（n=261）,杂合子强代谢型组占44.4%（n=272）,弱代谢型组占12.9%（n=78）。高水平FIB组的TT水平与正常水平FIB组比较差异无统计学意义（P=0.400 8）;无论是纯合子还是杂合子,cyp2c19基因强代谢型均比cyp2c19基因弱代谢型对氯吡格雷抗凝效应更敏感（P〈0.05）。结论高水平FIB对氯吡格雷抗凝效应并无显著影响;cyp2c19基因多态性对氯吡格雷的抗凝效应有显著影响,有助于临床指导用药,降低冠状动脉血栓发生率。

Objective To investigate the relationship between cyp2c19 gene polymorphisms and high concentration of fibrinogen with clopidogrel anticoagulation effect in the patients with coronary atherosclerotic heart disease（CAHD）.Methods A total of 611 CAHD patients taking oral clopidogrel in our hospital from May 2015 to November 2015 were selected and their cyp2c19 gene characteristics and the fibrinogen（FIB）levels were analyzed.The patients were divided into the cyp2c19 gene homozygote strong metabolism group（n=261）,heterozygote strong metabolim group（n=272）and weak metabolism group（n=78）.In all the cases,408 cases were detected the coagulation indicators and divided into the high FIB level group（n=116）,normal FIB level group（n=224）and low FIB level group（n=68）;then re-divided into the cyp2c19 gene weak metabolism and high FIB level group（n=24）,the cyp2c19 gene homozygote strong metabolism and high FIB level group（n=48）and cyp2c19 gene heterozygote strong metabolism and high FIB level group（n=48）.The thrombin time（TT）was compared among 3groups.Results cyp2c19 genotypes were＊1/＊1,＊1/＊2,＊1/＊3,＊2/＊2,＊2/＊3and ＊3/＊3.The gene chip detection found that the above genotypes had 261cases（42.7%）of cyp2c19＊1/＊1,235cases（38.4%）of cyp2c19＊1/＊2,6% 37 cases（6.0%）of cyp2c19＊1/＊3,60 cases（9.8%）of cyp2c19＊2/＊2,17cases（2.9%）of cyp2c19＊2/＊3and 1case（0.2%）of cyp2c19＊3/＊3.The cyp2c19 ＊1,＊2and ＊3allele frequencies were 65.0%（794/1 222）,30.5%（373/1 222）and 4.5%（55/1 222）respectively;The homozygote strong metabolism group accounted for 42.7%（n=261）,the heterozygote strong metabolism group accounted for 44.4%（n=272）and the weak metabolism group accounted for 12.9%（n=78）.The TT level had no statistical difference between the high FIB level group and the normal FIB level group（P=0.400 8）;no matter homozygote or heterozygote,the cyp2c19 gene strong metabolism type had more sensitivity to the clopidogrel anticoagulation effect than the cyp2c19 gene weak metabolism type（P〈0.05）.Conclusion The high FIB level has no influence to the clopidogrel anticoagulation effect;the cyp2c19 gene polymorphisms have significant influence on clopidogrel anticoagulation effect,which is conducive to clinical medication guidance and reduce the occurrence rate of coronary arterial thrombus.