Back to Search
Start Over
Common genetic variation near the phospholamban gene is associated with cardiac repolarisation
- Publication Year :
- 2009
-
Abstract
- To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1×10-6. To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4×10-83) and the phospholamban (PLN) gene (P = 1.9×10-29). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death.
Details
- Database :
- OAIster
- Notes :
- application/pdf, PLoS ONE vol. 4 no. 7, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.ocn929963529
- Document Type :
- Electronic Resource
- Full Text :
- https://doi.org/10.1371.journal.pone.0006138