Research CYP2C19*2Gene Distribution With Acute Coronary Syndrome

Objective：Cytochrome P450(cytochrome P450or CYP450, hereinafterreferred to as CYP) is a group of ferroheme enzymes, and the researchersfound that it is located liver microsome, and it metabolizes endogenous andexogenous material (include drugs, poisons, carcinogens, etc).CYP2C19enzyme is very important metabolic enzyme in this enzyme system, and it canmetabolize a wide variety of drugs, including anti-platelet aggregation drugs,proton pump inhibitors, diabetes, cancer drugs. CYP2C19gene has geneticpolymorphism, which presents with different metabolism and has differencesin individuals. A marked interindividual difference has been reported inCYP2C19activity. The research show normal homozygous genotypesCYP2C19*1/*1represent for extensive metabolizer, mutation homozygousgenotypes CYP2C19*2/*2represent for poor metabolizer, heterozygotegenotypes CYP2C19*1/*2represent for intermediate metabolizer. Clopidogrel,a2nd-generation P2Y12ADP receptor antagonist, is new antiplatelet drugs,which recommended for patients with coronary heart disease by the worldguidelines, and it is one of the components dual antiplatelet therapy. Howeverresearchers found that clopidogrel exerts little antiplatelet effect in a certainproportion of patients recently, a phenomenon termed "clopidogrel resistance".CYP2C19*2gene have been shown to be primarily responsible for themetabolic activation of clopidogrel. At present, genotype distribution andallele frequency of CYP2C19were explored in health the Han nationality anda part of minority population by literatures reported. But only a few literaturesreport that CYP2C19gene polymorphism distribute in patients. Few literaturereports that CYP2C19gene polymorphism distribute in patients with acutecoronary syndrome. The purpose of this research is to explore CYP2C19*2gene in patients with acute coronary syndrome, furthermore realize distribution of CYP2C19*2genotype with acute coronary syndrome. And thenwe calculated and compared genotype and allele frequency in different gender.Clinicians can choose the right drug and rationally adjust the drug dose, byrealizing genotype with acute coronary syndrome and judging indirectmetabolic patterns.Methods：The study includes264patients with acute coronary syndromeat the Cardiovascular Department, the Second Affiliated Hospital of Hebeimedical university, including185males,79females, aged29~79years(November2010until November2011). Patients were diagnosed with acutecoronary syndrome, by symptoms, signs and other related auxiliaryexamination (ECG, myocardial enzyme, muscle calcium protein,echocardiogram, etc). CYP2C19*1,*2were analyzed by polymerase chainreaction (PCR) and molecular hybrid technology. Then we calculatedgenotype and allele frequency. Then, all patients were divided into two groupsof gender (male group and female group), then we compared genotype andallele frequency. All data were analyzed using SPSS13.0statistical software.Results：1General conditionIn total264patients were selected, including185males and79females,aged29~79years, mean aged (57.43±9.72) years, complication high bloodpressure of170patients (64.4%), complication diabetes mellitus39patients(14.8%), Smokers134(50.8%), body mass index (BMI)＞24kg/m2of95patients (36.0%)2CYP2C19genotype and allele frequencyThe analysis results: CYP2C19*1/*1genotype:129patients (48.9%).CYP2C19*2/*2genotype:29patients (11.0%). Alleles*1:68.9%. Alleles*2:31.1%.3CYP2C19genotype and allele frequency distribution in different genderMale185patients: CYP2C19*1/*1genotype:86patients (46.5%),CYP2C19*1/*2genotype:79patients (42.7%), CYP2C19*2/*2genotype:20patients (10.8%),alleles*1：67.8%,alleles*2：32.2%. Female79patients: CYP2C19*1/*1genotype:43patients (54.4%),CYP2C19*1/*2genotype:27patients (34.2%), CYP2C19*2/*2genotype:9patients (11.4%); alleles*1:71.5%, alleles*2:28.5%.Genotype CYP2C19*1/*1, CYP2C19*1/*2and CYP2C19*2/*2frequency is no statistically different in different gender (X2=1.734, P=0.420＞0.05). Alleles*1,*2frequency is no statistical difference in differentgender (X2=1.524, P=0.217＞0.05).Conclusion:1Normal homozygous genotype CYP2C19*1/*1：48.9%, heterozygousgenotype CYP2C19*1/*2:40.1%, homozygous mutant genotype:CYP2C19*2/*2:11.0%in patients with acute coronary syndrome. Carrying mutations*2patients accounted for51.1%in patients with ACS,advise application largedoses of clopidogrel with less clopidogrel resistance happen.2Different gender genotype CYP2C19*1/*1, CYP2C19*1/*2andCYP2C19*2/*2frequency is no statistically different and alleles*1,*2frequency is no statistical difference.