Pharmacogenetic interactions between ABCB1 and SLCO1B1 tagging SNPs and the effectiveness of statins in the prevention of myocardial infarction.
Peters BJM., Rodin AS., Klungel OH., van Duijn CM., Stricker BHC., van't Slot R., de Boer A., Maitland-van der Zee A-H.
Genetic variability within the SLCO1B1 and ABCB1 transporter genes has been associated with modification of statin effectiveness in cholesterol management.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.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.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.