Association of TyG-BMI and malnutrition with reduced survival outcomes in patients with cancer: a prospective study.

Prolongation of the QT interval on the electrocardiogram reflects delayed ventricular repolarization and can predispose to potentially fatal arrhythmias such as torsades de pointes (TdP). Drug‐induced QT prolongation (diQTP) is a recognized adverse reaction across many therapeutic classes and is a leading cause of regulatory withdrawal or the addition of boxed warnings for otherwise effective agents. Clinical risk factors include female sex, electrolyte abnormalities, and heart failure, yet not all patients with these features develop prolonged QT, suggesting a genetic component []. Genetic variants associated with increased risk for diQTP have been identified. However, most were reported in studies with small sample sizes and therefore require validation in larger sample sizes to establish clinical relevance. In a prior review of pharmacogenomic predictors of diQTP, the rs10494366 T > G intronic variant was classified as having “limited evidence” for association with drug‐induced QTP []. This designation highlights the need for replication in independent, well‐powered cohorts. The gene encodes the nitric oxide synthase 1 adaptor protein, which interacts with neuronal nitric oxide synthase and influences cardiac calcium signaling and repolarization []. Several studies have shown that common variants, including rs10494366 (T > G), are associated with longer baseline QT intervals in population cohorts and in patients with long QT syndrome [, , , ]. However, its impact on drug‐induced QT changes remains uncertain [, , , , , , , , , ]. This analysis aimed to determine whether the G allele confers additional risk for QTc prolongation during a prescription for a high‐risk QT‐prolonging drug in a large biobank cohort with European ancestry. The rs10494366 variant is more common in populations of European ancestry and has been studied predominantly in European cohorts, providing the rationale for the ancestry‐specific focus of the present analysis.