Journal
PHARMACOGENOMICS JOURNAL
Volume 13, Issue 4, Pages 325-329Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2012.14
Keywords
adverse drug reaction; next-generation sequencing; sudden cardiac death
Categories
Funding
- Lung GO Sequencing Project [HL-102923]
- WHI Sequencing Project [HL-102924]
- Broad GO Sequencing Project [HL-102925]
- Seattle GO Sequencing Project [HL-102926]
- Heart GO Sequencing Project [HL-103010]
- National Institutes of Health [U01 HL65962, GM007569]
- trans-Atlantic network alliance grant from the Fondation Leducq ('Preventing Sudden Cardiac Death')
Ask authors/readers for more resources
Marked prolongation of the QT interval and polymorphic ventricular tachycardia following medication (drug-induced long QT syndrome, diLQTS) is a severe adverse drug reaction (ADR) that phenocopies congenital long QT syndrome (cLQTS) and is one of the leading causes for drug withdrawal and relabeling. We evaluated the frequency of rare non-synonymous variants in genes contributing to the maintenance of heart rhythm in cases of diLQTS using targeted capture coupled to next-generation sequencing. Eleven of 31 diLQTS subjects (36%) carried a novel missense mutation in genes with known congenital arrhythmia associations or with a known cLQTS mutation. In the 26 Caucasian subjects, 23% carried a highly conserved rare variant predicted to be deleterious to protein function in these genes compared with only 2-4% in public databases (P<0.003). We conclude that the rare variation in genes responsible for congenital arrhythmia syndromes is frequent in diLQTS. Our findings demonstrate that diLQTS is a pharmacogenomic syndrome predisposed by rare genetic variants.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available