학술논문

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group
Document Type
article
Source
The Pharmacogenomics Journal. 18(1)
Subject
Pharmacology and Pharmaceutical Sciences
Biomedical and Clinical Sciences
Genetics
Cardiovascular
Human Genome
Heart Disease
Patient Safety
Clinical Research
Good Health and Well Being
Aged
Cardiovascular Diseases
Cytochrome P-450 CYP2C9
Diabetes Mellitus
Type 2
Drug-Related Side Effects and Adverse Reactions
Electrocardiography
Ethnicity
Female
Genetic Variation
Genome-Wide Association Study
Humans
Male
Middle Aged
Pharmacogenetics
Pharmacogenomic Testing
Sulfonylurea Compounds
Pharmacology & Pharmacy
Pharmacology and pharmaceutical sciences
Language
Abstract
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P