http://www.cnr.it/ontology/cnr/individuo/prodotto/ID37271
Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta- Analysis of Three Genome-Wide Association Studies (Articolo in rivista)
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- Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta- Analysis of Three Genome-Wide Association Studies (Articolo in rivista) (literal)
- Anno
- 2009-01-01T00:00:00+01:00 (literal)
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- I M Nolte, et al (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
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- ISI Web of Science (WOS) (literal)
- Titolo
- Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta- Analysis of Three Genome-Wide Association Studies (literal)
- 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<1x10-6. 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 = 1.4x10-83) and the phospholamban (PLN) gene (P = 1.9x10-29). 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. (literal)
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