No association between CYP3A4*22 and statin effectiveness in reducing the risk for myocardial infarction

Pharmacogenomics. 2014 Aug;15(11):1471-7. doi: 10.2217/pgs.14.90.

Abstract

Aim: Genetic variation has been shown to influence statin response in terms of lowering LDL cholesterol. The recently discovered CYP3A4*22 allele (defined as rs35599367) has been shown to affect statin-induced LDL cholesterol lowering. Our objective was to investigate whether this polymorphism modifies the risk reduction for myocardial infarction (MI) by statins.

Patients & methods: We analyzed the interaction between the *22 minor allele and statin use in the independent Utrecht Cardiovascular Pharmacogenetics study and Rotterdam Study, using logistic and Cox regression models.

Results: In total, 771 MI cases and 6131 controls were included in the analyses. There was no effect of the CYP3A4*22 allelic status in the studies separately, nor when the estimates from both studies were combined (interaction odds ratio: 1.27; 95% CI: 0.73-2.21; p = 0.40 for carriers of the minor T-allele).

Conclusion: We found no association of the CYP3A4*22 minor allele (rs35599367) with the effectiveness of statins in reducing MI risk.

Keywords: CYP3A4; CYP3A4*22; myocardial infarction; pharmacogenetics; rs35599367; statins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Case-Control Studies
  • Cytochrome P-450 CYP3A / genetics*
  • Female
  • Genetic Variation / genetics*
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics*
  • Pharmacogenetics / methods
  • Risk

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human