RT Journal Article SR Electronic T1 ABCB1 gene variants, digoxin and risk of sudden cardiac death in a general population JF Heart JO Heart FD BMJ Publishing Group Ltd and British Cardiovascular Society SP 1973 OP 1979 DO 10.1136/heartjnl-2014-307419 VO 101 IS 24 A1 Maartje N Niemeijer A1 Marten E van den Berg A1 Jaap W Deckers A1 Adrianus L H J Aarnoudse A1 Albert Hofman A1 Oscar H Franco A1 André G Uitterlinden A1 Peter R Rijnbeek A1 Mark Eijgelsheim A1 Bruno H Stricker YR 2015 UL http://heart.bmj.com/content/101/24/1973.abstract AB Objective The ATP-binding cassette B1 (ABCB1) gene encodes P-glycoprotein, a transport protein, which plays an important role in the bioavailability of digoxin. We aimed to investigate the interaction between variants within the ABCB1 gene and digoxin on the risk of sudden cardiac death (SCD).Methods Within the Rotterdam Study, a population-based cohort study in persons 45 years of age and older, we used Cox regression to analyse the association between three polymorphisms that have been associated with digoxin bioavailability, extracted from 1000-Genomes imputed ABCB1 genotypes and the risk of SCD, stratified by digoxin use.Results In a total study population of 10 932 persons, 419 SCDs occurred during a median follow-up of 9.8 years. In non-users of digoxin, the risk of SCD was not different across genotypes. In digoxin users, homozygous T allele carriers of C1236T (HR 1.90; 95% CI 1.09 to 3.30; allele frequency 0.43), G2677T (HR 1.89; 95% CI 1.10 to 3.24; allele frequency 0.44) and C3435T (HR 1.72; 95% CI 1.03 to 2.87; allele frequency 0.53) had a significantly increased risk of SCD in a recessive model. Interaction between the ABCB1 polymorphisms and digoxin use was significant for C1236T and G2677T in the age-adjusted and sex-adjusted model.Conclusions In this study, we showed that in digoxin users variant alleles at each of the three loci in the ABCB1 gene were associated with an increased risk of SCD compared with digoxin users with none or one T allele. If replicated, the findings imply that the ABCB1 genotype modifies the risk of cardiac digoxin toxicity.