OBJECTIVE: The purpose of this study was to use a candidate gene approach to identify common polymorphisms that are associated with resting sinus heart rate in a population without overt cardiovascular disease. BACKGROUND: Increased resting heart rate is significantly associated with susceptibility to development of myocardial infarction, sudden cardiac death, and overall cardiac mortality. METHODS: A longitudinal cohort of 1468 individuals (active and retired middle-aged Canadian firefighters) who were enrolled in the Firefighters and Their Endothelium (FATE) study was evaluated. Resting heart rate was recorded from the electrocardiogram (ECG) obtained at enrollment. Candidate genes were selected for their known roles in sinus node automaticity and/or its regulation, and single nucleotide polymorphisms (SNPs) with a minor allele frequency of > or =0.20 were targeted. A total of 53 SNPs in 46 genes were selected and analyzed in a screening sample, and 33 SNPs in 29 genes were evaluated in the full population. RESULTS: Univariate analysis detected five putative associations between HR and SNPs. As expected, environmental covariates were identified. Three polymorphisms, ADRB1 G389R, SCN5a H558R, and CASQ1 intron 2, remained statistically significant and independent of covariates. Some alleles were associated with higher and some with lower heart rates. A stepwise increase in heart rate was observed that was dependent on the number of tachycardia-associated alleles with progressive increases in mean heart rate from 51 to 66 bpm. CONCLUSIONS: Common polymorphisms are associated with heart rate in a stepwise allele-dependent manner.
OBJECTIVE: The purpose of this study was to use a candidate gene approach to identify common polymorphisms that are associated with resting sinus heart rate in a population without overt cardiovascular disease. BACKGROUND: Increased resting heart rate is significantly associated with susceptibility to development of myocardial infarction, sudden cardiac death, and overall cardiac mortality. METHODS: A longitudinal cohort of 1468 individuals (active and retired middle-aged Canadian firefighters) who were enrolled in the Firefighters and Their Endothelium (FATE) study was evaluated. Resting heart rate was recorded from the electrocardiogram (ECG) obtained at enrollment. Candidate genes were selected for their known roles in sinus node automaticity and/or its regulation, and single nucleotide polymorphisms (SNPs) with a minor allele frequency of > or =0.20 were targeted. A total of 53 SNPs in 46 genes were selected and analyzed in a screening sample, and 33 SNPs in 29 genes were evaluated in the full population. RESULTS: Univariate analysis detected five putative associations between HR and SNPs. As expected, environmental covariates were identified. Three polymorphisms, ADRB1G389R, SCN5aH558R, and CASQ1 intron 2, remained statistically significant and independent of covariates. Some alleles were associated with higher and some with lower heart rates. A stepwise increase in heart rate was observed that was dependent on the number of tachycardia-associated alleles with progressive increases in mean heart rate from 51 to 66 bpm. CONCLUSIONS: Common polymorphisms are associated with heart rate in a stepwise allele-dependent manner.
Authors: Mark Eijgelsheim; Christopher Newton-Cheh; Nona Sotoodehnia; Paul I W de Bakker; Martina Müller; Alanna C Morrison; Albert V Smith; Aaron Isaacs; Serena Sanna; Marcus Dörr; Pau Navarro; Christian Fuchsberger; Ilja M Nolte; Eco J C de Geus; Karol Estrada; Shih-Jen Hwang; Joshua C Bis; Ina-Maria Rückert; Alvaro Alonso; Lenore J Launer; Jouke Jan Hottenga; Fernando Rivadeneira; Peter A Noseworthy; Kenneth M Rice; Siegfried Perz; Dan E Arking; Tim D Spector; Jan A Kors; Yurii S Aulchenko; Kirill V Tarasov; Georg Homuth; Sarah H Wild; Fabio Marroni; Christian Gieger; Carmilla M Licht; Ronald J Prineas; Albert Hofman; Jerome I Rotter; Andrew A Hicks; Florian Ernst; Samer S Najjar; Alan F Wright; Annette Peters; Ervin R Fox; Ben A Oostra; Heyo K Kroemer; David Couper; Henry Völzke; Harry Campbell; Thomas Meitinger; Manuela Uda; Jacqueline C M Witteman; Bruce M Psaty; H-Erich Wichmann; Tamara B Harris; Stefan Kääb; David S Siscovick; Yalda Jamshidi; André G Uitterlinden; Aaron R Folsom; Martin G Larson; James F Wilson; Brenda W Penninx; Harold Snieder; Peter P Pramstaller; Cornelia M van Duijn; Edward G Lakatta; Stephan B Felix; Vilmundur Gudnason; Arne Pfeufer; Susan R Heckbert; Bruno H Ch Stricker; Eric Boerwinkle; Christopher J O'Donnell Journal: Hum Mol Genet Date: 2010-07-16 Impact factor: 6.150
Authors: E D Wittwer; Z Liu; N D Warner; D R Schroeder; A M Nadeau; A R Allen; C J Murillo; R L Elvebak; B M Aakre; J H Eisenach Journal: Auton Neurosci Date: 2011-07-31 Impact factor: 3.145
Authors: Christian Veltmann; Hector Barajas-Martinez; Christian Wolpert; Martin Borggrefe; Rainer Schimpf; Ryan Pfeiffer; Gabriel Cáceres; Elena Burashnikov; Charles Antzelevitch; Dan Hu Journal: J Am Heart Assoc Date: 2016-07-05 Impact factor: 5.501