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Updated: Aug 11, 2026
07:15
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation
Christina A Pippis1, Ana I Lopez-Medina1, Choudhary Anwar A Chahal2,3,4
1Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
Clinical and Translational Science
|August 10, 2026
Summary
The NOS1AP rs10494366 variant does not increase the risk of drug-induced QTc prolongation (diQTP) in patients taking high-risk medications. This genetic marker was not associated with diQTP in a large study of European ancestry individuals.
Area of Science:
- Pharmacogenomics
- Cardiovascular Genetics
- Drug Safety
Background:
- Drug-induced QTc prolongation (diQTP) is a significant risk factor for potentially fatal arrhythmias like torsades de pointes.
- Identifying genetic predispositions to diQTP is crucial for personalized medicine and improving drug safety.
- The NOS1AP rs10494366 T>G variant has been previously investigated for its association with baseline QTc interval, but its role in drug-induced effects requires further clarification.
Purpose of the Study:
- To investigate the association between the G allele of the NOS1AP rs10494366 variant and the risk of drug-induced QTc prolongation (diQTP).
- To evaluate whether carriers of the NOS1AP rs10494366 G allele are at higher risk for diQTP when exposed to high-risk QT-prolonging medications.
Main Methods:
- Retrospective case-control study utilizing the Michigan Genomics Initiative (MGI) biobank.
- Analysis included 5848 patients of European ancestry prescribed at least one high-risk QT-prolonging drug between 2001 and 2022.
- diQTP was defined by specific QTc interval changes (Bazett-corrected), and logistic regression (unadjusted and propensity-score-adjusted) was used to test associations with the rs10494366 variant.
Main Results:
- The minor allele frequency (G) for rs10494366 was 0.36, with genotype frequencies in Hardy-Weinberg equilibrium.
- diQTP occurred in 12.2% of the study participants.
- The G allele of NOS1AP rs10494366 was not significantly associated with an increased risk of diQTP, neither in unadjusted (OR 0.94, p=0.27) nor adjusted analyses (OR 0.94, p=0.30).
Conclusions:
- In a large, real-world cohort of European ancestry patients, the NOS1AP rs10494366 variant did not show a significant association with the risk of drug-induced QTc prolongation.
- These findings suggest that the previously observed links between this variant and baseline QTc may not directly translate to increased susceptibility to diQTP in all clinical settings.
- Further research may be needed to understand the complex genetic factors influencing diQTP.
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