Pharmacogenetic Interactions Between ABCB1 and SLCO1B1 Tagging SNPs and the Effectiveness of Statins in the Prevention of Myocardial Infarction

Abstract

Aims: Genetic variability within the SLCO1B1 and ABCB1 transporter genes has been associated with modification of statin effectiveness in cholesterol management. Materials & methods: We conducted a case–control study using a population-based registry of pharmacy records linked to the hospital discharge records. Within a hypercholesterolemic cohort, we included 668 myocardial infarction cases and 1217 controls. Results: We tested 24 tagging SNPs and found two SNPs within ABCB1 (rs3789244, p = 0.01; rs1922242, p = 0.01) to interact with statin treatment. In addition, we found a nonsignificant haplotype–treatment interaction (p = 0.054). The odds ratio for subjects homozygous for SLCO1B1*1A was 0.49 (95% CI: 0.34–0.71) compared with 0.31 (95% CI: 0.24–0.41) for heterozygous or noncarriers of the *1A allele. Conclusion: This is the first study to demonstrate that common genetic variability within the SLCO1B1 and ABCB1 genes is associated with the modification of the effectiveness of statins in the prevention of the clinical outcome, myocardial infarction.

KEYWORDS::

• ABCB1
• case–control study
• drug transporter
• myocardial infarction
• pharmacogenetics
• pharmacogenomics
• SLCO1B1
• statins

Financial & competing interests

The division of Pharmacoepidemiology and Pharmacotherapy, employing authors Bas Peters, Olaf Klungel, Anthonius de Boer and Anke-Hilse Maitland-van der Zee, has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private-public funded Top Institute Pharma(www.tipharma.nl, includes cofunding from universities, government and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health. Anke-Hilse Maitland-van der Zee is funded by a Veni grant from the Netherlands Organization for Scientific Research (NWO). Andrei S Rodin is funded by the grants from PhRMA foundation, NIH, Gilson-Longenbaugh foundation and UTHSCH Office of Biotechnology Seed Grant Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The division of Pharmacoepidemiology and Pharmacotherapy, employing authors Bas Peters, Olaf Klungel, Anthonius de Boer and Anke-Hilse Maitland-van der Zee, has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private-public funded Top Institute Pharma(www.tipharma.nl, includes cofunding from universities, government and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health. Anke-Hilse Maitland-van der Zee is funded by a Veni grant from the Netherlands Organization for Scientific Research (NWO). Andrei S Rodin is funded by the grants from PhRMA foundation, NIH, Gilson-Longenbaugh foundation and UTHSCH Office of Biotechnology Seed Grant Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.