Pharmacogenetic interactions between ABCB1 and SLCO1B1 tagging SNPs and the effectiveness of statins in the prevention of myocardial infarction.
OBJECTIVE
Genetic variability within the SLCO1B1 and ABCB1 transporter genes has been associated with modification of statin effectiveness in cholesterol management.


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.


CONCLUSIONS
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.
Peters
Bas J M
BJ
Faculty of Science, Division of Pharmacoepidemiology & Pharmacotherapy, Utrecht University, Utrecht, The Netherlands.
Rodin
Andrei S
AS
Klungel
Olaf H
OH
van Duijn
Cornelia M
CM
Stricker
Bruno H Ch
BH
van't Slot
Ruben
R
de Boer
Anthonius
A
Maitland-van der Zee
Anke-Hilse
AH
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D027381:Liver-Specific Organic Anion Transporter 1; D016015:Logistic Models; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D027361:Organic Anion Transporters / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human