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

Maarten Leusink*, Catherine E. De Keyser, N. Charlotte Onland-Moret, Albert Hofman, Loes E. Visser, Bruno H. Stricker, Paul I W De Bakker, Anthonius De. Boer, Ron H N Van Schaik, Anke Hilse Maitland-Van Der Zee

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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. Original submitted 9 April 2014; Revision submitted 30 May 201.

Original languageEnglish
Pages (from-to)1471-1477
Number of pages7
JournalPharmacogenomics
Volume15
Issue number11
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • CYP3A4
  • CYP3A4∗22
  • myocardial infarction
  • pharmacogenetics
  • rs35599367
  • statins

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