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Race-based gene variations affect mortality risk among clopidogrel users
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Several mutations of cytochrome P450 isoenzymes are associated with increased risk for mortality in patients taking clopidogrel after acute MI; however, the specific mutations and mechanisms of action vary by race, according to new study findings.
Researchers genotyped 2,732 patients (2,062 white, 670 black) who were hospitalized for acute MI for cytochrome P450 (CYP) polymorphisms. Participants included were enrolled in the prospective, multicenter TRIUMPH study who were discharged alive and of either black or white race.
Sharon Cresci, MD, from the Washington University School of Medicine in St. Louis, and colleagues investigated whether certain CYP variants were associated with different rates of 1-year mortality in patients discharged on clopidogrel. Seventy-nine percent of white patients and 64.4% of black patients from the study were discharged on clopidogrel, which must be converted into its active metabolite via multiple CYP isoenzymes to work.
For white patients, carrying the loss-of-function CYP2C19*2 allele was associated with an increase in 1-year mortality (adjusted HR=1.7; 95% CI, 1.01-2.86). The researchers also observed a trend toward increased rate of recurrent MI in that cohort (adjusted HR=2.1; 95% CI, 0.95-4.63).
For black patients, carrying the gain-of-function CYP2C19*17 allele was associated with an increase in 1-year mortality (adjusted HR for *1/*17 vs. *1/*1=2.02; 95% CI, 0.92-4.44; adjusted HR for *17/*17 vs. *1/*1=8.97; 95% CI, 3.34-24.1), as was carrying the CYP2C19*1C allele (adjusted HR for *1/*1C vs. *1/*1=1.89; 95% CI, 0.85-4.22; adjusted HR for *1C/*1C vs. *1/*1=4.96; 95% CI, 1.69-14.56), according to the results.
Black patients discharged on clopidogrel carrying the CYP2C19*1C allele were also at higher risk for bleeding compared with those not carrying it (OR=2.9; 95% CI, 1.416-5.937 for heterozygotes; OR=2.97; 95% CI, 0.644-13.646 for homozygotes), the researchers found.
“The research is provocative,” Cresci said in a press release. “Knowing about potential genetic differences based on race can help physicians tailor drugs to patients based on their genetic makeup. There [was] almost no data, until now, about these variants in African Americans.”
Disclosure: The study was funded by the NIH. See the full study for a list of the researchers’ relevant financial disclosures.
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