| Part ? Distribution difference of CYP2C19,ABCB1 C3435T,PON1 L55M,and PON1 Q192R gene polymorphism between East-Asian and Euro-American populationsBackgrounds:Dual antiplatelet therapy with aspirin and clopidogrel is needed for treatment of patients with acute coronary syndrome(ACS)and those undergoing percutaneous coronary intervention(PCI).!n recent years,several genes definitely or probably associated with clopidogrel absorption and metabolism have caused some concern.Those genes include CYP2C19(cytochrome P450 2C19),ABCB1 C3435T(ATP-binding cassette,sub-family B,member 1),PON1 L55M and PON1 Q192R(paraoxonase-1).The purpose of this part was to explore those gene polymorphism distribution differences between East-Asian and Euro-American populations.Methods:From January 2005 to February 2009,a total of 2569 patients with a diagnosis of ACS within 4 weeks after the onset of symptoms presenting to Fuwai Hospital were enrolled in a gene database study.During hospitalization,important clinical characteristics were collected.All patients were draw blood to detect genotypes of CYP2C19*2-*8,*17,ABCB1 C3435T,PON1 L55M and PON1 Q192R by a TaqMan assay(PCR-LDR,ligase detection reaction).Allele frequency was estimated by gene counting.Combining our data and these from other East-Asian countries,we conducted a comparative analysis with results from Euro-American populations.Results:Distribution of LL,LM and MM genotypes for PON1 L55M were 91.9%,8.0%and 0.2%.For CYP2C19,heterozygote carrying one allele of*2,*3 and*4 was the most common genotypes in Asians(~48.8%),while more than half of the westerners were wild type(~71.2%)(*1/*1).For ABCB1 C3435T,the most common genotypes in Asians were CC(~46.6%)and CT(~48.6%),and TT(~18.2)was the least;in westerners,CT(~50%)was the most common genotype,followed by TT(29.1%),and CC(~23%)was the least.For PON1 Q192R,Asians had the most common genotype of QR(~47.8%),then RR(~42%),and the last QQ(~14.7%);westerners had totally reverse genotype distribution,in which the most common was QQ(~53.3%),followed by QR(~43.9%),and RR(~11%)was the least genotype.Conclusions:East-Asians have a totally different CYP2C19,ABCB1 C3435T,and PON1 Q192R gene polymorphism distributions from Euro-American populations.Part ? Relationships of CYP2C19,ABCB1 C3435T,PON1 L55M,and PON1 Q192R genotypes and in-stent restenosis and re-stenting in patients with acute coronary syndrome after coronary stentingBackgrounds:East-Asians have very different genotype distributions of cytochrome P450 2C19(CYP2C19),ATP-binding cassette,sub-family B,member 1(ABCB1)C3435T,paraoxonase-1(PON1)L55M,and PON1 Q192R from Euro-American populations.Many studies have explored the relationships of these genes and adverse events such as death,myocardial infarction,stroke,and stent thrombosis.The purpose of this study was to evaluate the effects of these genes on outcomes of in-stent restenosis and re-stenting in patients with acute coronary syndrome(ACS)after coronary stenting.Methods:A total of 2569 patients with ACS were enrolled in a gene database study.Among the 1674 patients receiving coronary stenting and dual antiplatelet therapy with clopidogrel and aspirin,504 patients performed repeated coronary angiography within the next year after discharge and were eligible to complete our final cohort.Results:The prevalence of the CYP2C19 loss-of-function carriers(had at least 1 allele of*2,*3 and*4)was considerable high(52.2%).During re-angiography,in-stent restenosis occurred in 102(20.2%)out of the 504 patients;the mean restenosis degree was 71.3%and 152(30.2%)patients received re-stenting treatment.In multivariate Logistic regression,only age(OR 1.03,95%Cl 1.01-1.05,p=0.019)and stent type(drug eluting stents versus bare metal stents:OR 0.16,95%CI 0.10-0.28,p<0.001)were significantly associated with in-stent restenosis.As for predictors of re-stenting,multivariate Logistic regression identified variables of left ventricular ejection fraction(LVEF)(OR 0.97,95%CI 0.95-0.99,p=0.021),treated by statin at baseline(OR 0.37,95%Cl 0.15-0.93,P=0.035),coronary artery lesions(triple vessel disease versus single vessel disease:OR 2.35,95%CI 1.35-4.08,P=0.002)and PON1 Q192R genotype(P=0.001).Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting compared with genotypes of QQ and QR(OR 2.09,95%CI 1.36-3.21,p=0.001).The genotypes of CYP2C19,ABCB1 C3435T,and PON1 L55M showed no significant associations with in-stent restenosis or re-stenting,Conclusions:Genotype RR of PONI Q192R was an independent risk factor predicting re-stenting in Chinese ACS patients after coronary stenting.Part ? Relationships of CYP2C19,ABCB1 C3435T,PON1 L55M,and PON1 Q192R genotypes and long-term all-cause death,target lesion revascularization,or acute myocardial infarction in patients with acute coronary syndromeBackgrounds:Many recent studies have explored the relationships of CYP2C19(cytochrome P450 2C19),ABCB1 C3435T(ATP-binding cassette,sub-family B,member 1),PON1 L55M(paraoxonase-1),and PON1 Q192R polymorphisms and the on-clopidogrel platelet reactivity or subsequent adverse cardiovascular events,and came to inconsistent outcomes.Most of these studies reported clinical results of short-term ischemic events or stent thrombosis,and studies focused on long-term adverse events were limited.The purpose of this study was to evaluate the effects of these genes on outcomes of long-term all-cause death,target lesion revascularization,and acute myocardial infarction in Chinese Beijing patients with acute coronary syndrome(ACS).Methods:A total of 2569 ACS patients were enrolled in a gene database study,among whom 1279 patients were Beijing residents(24 died in the hospital at baseline).From February 2015 to July 2017,the remaining 1255 Beijing patients were investigated in chronological order by reviewing inpatient and outpatient medical records,and telephone follow-up.During investigation,adverse cardiovascular events including all-cause death(cardiac and noncardiac),target lesion revascularization(PCI and/or CABG),and acute myocardial infarction,as well as the dates of events were recorded.Through multivariate Logistic and COX regression models we analyzed the correlation of baseline characteristics and different genotypes with the long-term adverse events.Results:Finally 800 Beijing patients were successfully followed.The composite event of all-cause death,target lesion revascularization,or acute myocardial infarction occurred in 467 patients(59.5%),and the median follow-up period was 9 years.As for secondary endpoints,31.9%patients experienced target lesion revascularization,25.4%patients died,and 12.9%patients suffered acute myocardial infarction.In multivariate COX regression,age(OR 1.01,95%CI 1.00-1.02,P=0.036),left ventricular ejection fraction(LVEF)(OR 0.98,95%CI 0.97-0.99,P<0.001),treated by PCI at baseline(OR 0.79,95%CI 0.64-0.98,P=0.033),treated by CABG at baseline(OR 0.32,95%CI 0.19-0.53,P<0.001)were significantly associated with the composite event.The impact of CYP2C19 genotype on composite event was revealed that only patients carrying mutation homozygote had significant higher risk than patients with mutant heterozygote(OR 1.48,95%CI 1.04-2.10,P=0.030).For the secondary endpoints,multivariate Logistic regression only identified patients carrying mutation homozygote(OR 2.27,95%CI 1.19-4.32,P=0.013)had significant higher risk of acute myocardial infarction than patients with mutant heterozygote and wild type.The genotypes of PON1 L55M,PON1 Q192R,and ABCB1 C3435T showed no significant associations with long-term adverse events.Conclusions:Advanced age was a risk factor of long-term composite enents for Chinese Beijing patients with ACS,while higher LVEF and treated by PCI or CABG at baseline were protective factors.Thus,coronary revascularization is the decisive factor in improving the long-term prognosis of ACS patients.Effect of CYP2C19 on composite event was revealed that only patients carrying mutation homozygote had significant higher risk than patients with mutant heterozygote. |
PDF Full Text Request