title: Cytochrome P450 2C19*2 polymorphism in patients with stable coronary heart disease and risk for secondary cardiovascular disease events: results of a long-term follow-up study in routine clinical care.
abstract: BACKGROUND
  CYP2C19*2 polymorphism is related to metabolizer phenotypes resulting in reduced effectiveness in converting the antiplatelet drug clopidogrel to active drug. An association of the genotype itself with adverse outcomes is discussed. We investigated the prognostic value of carriage of the CYP2C19*2 allele in a high risk group of patients with prevalent coronary heart disease (CHD) at baseline during long-term follow-up under conditions of routine clinical care.
  
  
  METHODS
  In n=1050 patients with stable CHD at baseline genotyping of CYP2C19 allele *2 (rs4244285; 681G>A) was performed. The Cox-proportional hazards model was employed to investigate the association of CYPC19*2 allele status with cardiovascular disease (CVD) events during eight year follow-up. The analysis was also performed in patients who did not take clopidogrel or ticlopidin.
  
  
  RESULTS
  Only the very few patients homozygous for a loss-of-function variant of CYP2C19, allele *2 (2.6%), had a statistically significantly higher incidence rate for secondary CVD events during long-term follow-up than wild-type carriers (50.8 versus 21.5 per 1000 patients years; rate for heterozygous carries 17.2 per 1000 patient years). The hazard ratio after adjustment for covariates compared to the wild-type carriers was 2.59 (95% confidence interval (CI) 1.27-5.28) and 0.80 (95% CI 0.52-1.23) for homozygous and heterozygous allele carriers, respectively.
  
  
  CONCLUSIONS
  In this medium-size group of patients with stable CHD homozygous carriers of the loss-of-function allele CYP2C19*2 were at increased risk for subsequent CVD events during 8 year follow-up independent of other risk factors. As only few patients carried the homozygous loss-of-function variant and we found overall no evidence for improved clinical utility, a benefit of genotyping in this patient population seems unlikely.
authors: Institute of Epidemiology and Medical Biometry, Ulm University, Helmholtzstr 22, Ulm D-89081, Germany. dietrich.rothenbacher@uni-ulm.de.
authors: Dietrich
authors: D
authors: Rothenbacher
authors: Michael M
authors: MM
authors: Hoffmann
authors: Lutz P
authors: LP
authors: Breitling
authors: Iris
authors: I
authors: Rajman
authors: Wolfgang
authors: W
authors: Koenig
authors: Hermann
authors: H
authors: Brenner
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D003327:Coronary Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
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