Document Detail


Common candidate gene variants are associated with QT interval duration in the general population.
MedLine Citation:
PMID:  19019189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30-40% of the QT-interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population-based sample.
METHODS: We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5043 Finnish individuals, using Sequenom MALDI-TOF mass spectrometry. ECG parameters were measured from digital 12-lead ECGs and QT intervals were adjusted for age, gender and heart rate with a nomogram (Nc) method derived from the present study population.
RESULTS: The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QT(Nc) interval (P=3.6 x 10(-11)) in gender-pooled analysis. In agreement with previous studies, we replicated the association with QT(Nc) interval with minor alleles of KCNH2 intronic SNP rs3807375 [1.6 ms (SE 0.4) or 0.08 SD, P=4.7 x 10(-5)], KCNH2 K897T [-2.6 ms (SE 0.5) or -0.14 SD, P=2.1 x 10(-7)] and NOSA1P variants including rs2880058 [4.0 ms (SE 0.4) or 0.22 SD, P=3.2 x 10(-24)] under additive models.
CONCLUSIONS: We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age-, gender- and heart rate-adjusted QT interval and could thus modulate repolarization-related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.
Authors:
A Marjamaa; C Newton-Cheh; K Porthan; A Reunanen; P Lahermo; H Väänänen; A Jula; H Karanko; H Swan; L Toivonen; M S Nieminen; M Viitasalo; L Peltonen; L Oikarinen; A Palotie; K Kontula; V Salomaa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-25
Journal Detail:
Title:  Journal of internal medicine     Volume:  265     ISSN:  1365-2796     ISO Abbreviation:  J. Intern. Med.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-20     Completed Date:  2009-06-18     Revised Date:  2013-04-11    
Medline Journal Info:
Nlm Unique ID:  8904841     Medline TA:  J Intern Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  448-58     Citation Subset:  IM    
Affiliation:
Research Program in Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics*
Adult
Aged
Aged, 80 and over
Cluster Analysis
Death, Sudden, Cardiac / etiology
Electrocardiography
Ether-A-Go-Go Potassium Channels / genetics
Female
Finland / epidemiology
Genetic Variation / genetics*
Genotype
Humans
Long QT Syndrome / epidemiology,  genetics*,  physiopathology
Male
Middle Aged
Polymorphism, Single Nucleotide*
Potassium Channels, Voltage-Gated / genetics*
Grant Support
ID/Acronym/Agency:
089061//Wellcome Trust; 089062//Wellcome Trust; K23 HL080025-04/HL/NHLBI NIH HHS; K23HL080025/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Ether-A-Go-Go Potassium Channels; 0/KCNE1 protein, human; 0/NOS1AP protein, human; 0/Potassium Channels, Voltage-Gated
Comments/Corrections

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