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.

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Keywords CYP3A4, CYP3A4∗22, myocardial infarction, pharmacogenetics, rs35599367, statins
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Journal Pharmacogenomics
Leusink, M, de Keyser, C.E, Onland-Moret, N.C, Hofman, A, Visser, L.E, Stricker, B.H.Ch, … Maitland-van der Zee, A-H. (2014). No association between CYP3A4∗22 and statin effectiveness in reducing the risk for myocardial infarction. Pharmacogenomics, 15(11), 1471–1477. doi:10.2217/pgs.14.90