ABCB1 gene variants, digoxin and risk of sudden cardiac death in a general population.

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.

Genetic variation in NOS1AP is associated with sudden cardiac death: evidence from the Rotterdam Study.

Common variation within the nitric oxide-1 synthase activator protein (NOS1AP) locus is strongly related to QT interval, a sudden cardiac death (SCD) risk factor. A recent report describes common variation in NOS1AP associated with SCD in a US population of European ancestry. The objective of the current study was to obtain additional evidence by investigating the association between NOS1AP variants and SCD in the prospective population-based Rotterdam Study.

Identification of a common variant at the NOS1AP locus strongly associated to QT-interval duration.

QT-interval prolongation is an electrophysiologic phenomenon associated with sudden cardiac death. The QT-interval in the general population is approximately 35% heritable. In genome-wide association studies, a common variant (rs10494366T > G) within the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was identified and consistently associated with QT-interval duration.

Age- and gender-specific incidence of hospitalisation for digoxin intoxication.

Background: The safety of digoxin (digitalis) therapy has greatly improved over the past three decades, but recent incidence rates for digoxin intoxication-related hospitalisation are not available. Recent literature suggests that women are at higher risk of digoxin toxicity.

Objective: To provide age- and gender-specific incidence rates for digoxin intoxication-related hospitalisation and mortality during digoxin intoxication-related hospitalisation in The Netherlands in the period 2001-4.