Correlation Of Cytochrome P450 2C19 Gene Polymorphism And Risk Of Gastrointestinal Bleeding (GIB) In Coronary Heart Disease (CHD) Patients On Dual Antiplatelet Therapy After Percutaneous Coronary Interventions (PCI)

Objective:To research correlation between Cytochrome P450 2C19 gene polymorphism and risk of gastrointestinal bleeding of coronary heart disease patients on dual antiplatelet therapy after percutaneous coronary intervention(PCI),and to explore the influence of CYP2C19*2,CYP2C19*3 mutation on clopidogrel metabolism,and to explore the risk factors for gastrointestinal bleeding in patients accepting dual antiplatelet therapy.Which were helpful to guide the use of antiplatelet drugs,reduce gastrointestinal bleeding.Methods: A total of 532 patients underwent successful coronary stenting and involved clopidogrel and aspirin standardly were included.Those patients’ general clinical datas,such as including age,gender,blood pressue,blood fat,smoking,diabetes,peptic ulcer,earlier history of GIB,history of h.pylori infection,statin using were recorded.CYP2C19*1,CYP2C19*2 and CYP2C19*3 genotyping were performed.All patients were divided into three groups according to their metabolic type: Extensive metabolizer,Intermediate metabolizer and Poor metabolizer.Platelet inhibition ratio was measured by thromboelasto graphy 3 months later.During the 12-month follow-up period,the author recorded those patients’ records of reentry,telephone,or monthly fecal occult blood tests,month-ly routine blood tests.Results: Of 532 patients were involved in the study,504 finish the study.The average age was(62.19±7.22).There were 340(67.5%)males and 164(32.5%)females.According to CYP2C19 genotype,patients were divided into 3 groups: Extensive metabolizers(EM),including 257 patients,account for 51.0%;Intermediary metabolizers(IM),including 216 patients,account for 42.9%;and Poor metabolizers(PM),including 31 patients,account for 6.2%.No differences were found in age,gender,smoking,diabetes,hypertension or hyperlipidemia among these 3 proups.At the same time,no differences are observed in risk factors of GIB(peptic ulcer,earlier history of GIB,history of h.pylori infection);no differences are observed in using of statins;no differences were found in platelet aggregation inhibition rate by AA.Among the patients included this study,257 patients with the genotype of CYP2C19*1/*1,accounting for 51.0%;167 patients with the genotype of CYP2C19*1/*2,accounting for 33.1%;49 patients with the genotype of CYP2C19*1/*3,accounting for 10.0%;23 patients with the genotype of CYP2C19*2/*2,accounting for 33.1%;5 patients with the genotype of CYP2C19*2/*3,accounting for 1.0%;3 patients with the genotype of CYP2C19*3/*3,accounting for 0.6%.The frequency of CYP2C19*1 was 72.7%,CYP2C19*2 was 21.7%,CYP2C19*3 is 6.0%.Distribution of CYP2C19 genotype was in conformity with Hardy Weinberg equilibrium,which means those patients come from a large and random mating population.Platelet aggregation inhibition rate by ADP in Extensive metabolizers is 56.2±5.3%,intermediate metabolizers’ is 47.2±9.0%,poor metabolizers’ is 44.6±9.2%.Platelet aggregation inhibition rate by ADP is significantly different among these three groups.During the follow-up periods,32 patients in EM encountered gastrointestinal hemorrhage,accounting for 12.5%,and 13 patients in IM encountered gastrointestinal hemorrhage,accounting for 6.02%,ang 2 patients in PM encountered gastrointestinal hemorrhage,accounting for 6.45%.The rates of gastrointestinal bleeding in three groups are statistically difference(P < 0.05),and the incidence of gastrointestinal bleeding in EM is obviously higher than other two groups.Using Logistic regression model to analyze the related factors influencing the happen of gastrointestinal hemorrhage,it was found the following facts significantly increased risk of gastrointestinal hemorrhage: age,smoking,metabolic type,history of gastrointestinal bleeding,history of peptic ulcer and infection of helicobacter pylori.Conclusions:1 In patients with coronary artery disease,who underwent PCI,CYP2C19 gene polymorphisms affect the efficacy of clopidogrel antiplatelet,the platelet aggregation inhibition rates of ADP with CYP2C19*2 and CYP2C19* 3 allele were lower than the non-mutation genotype.2 For patients with coronary heart disease,CYP2C19 gene polymorphisms is associated with the occurrence of gastrointestinal bleeding,gastrointestinal bleeding events with CYP2C19*2 and CYP2C19*3 allele were more than non-mutation genotype.3 For patients with coronary heart disease,accepted aspirin and clopidogrel dual antiplatelet therapy after PCI,the emergence of gastrointestinal bleeding correlates with age,smoking,metabolic type,history of gastrointestinal bleeding,history of peptic ulcer and infection of helicobacter pylori,and no correlate with gender,hypertension,history of diabetes,hyperlipidemia.