The Genetic Contribution to Heart Rate and Heart Rate Variability in Quiescent Mice

Overview

Journal Am J Physiol Heart Circ Physiol

Publisher American Physiological Society

Specialties Cardiology & Vascular Diseases
Physiology

Date 2008 May 6

PMID 18456734

Citations 17

Authors

Reuben Howden

Eric Liu

Laura Miller-DeGraff

Heather L Keener

Christopher Walker

James A Clark

Page H Myers

D Clay Rouse

Tim Wiltshire

Steven R Kleeberger

Affiliations

Soon will be listed here.

Abstract

Recent studies have suggested a genetic component to heart rate (HR) and HR variability (HRV). However, a systematic examination of the genetic contribution to the variation in HR and HRV has not been performed. This study investigated the genetic contribution to HR and HRV using a wide range of inbred and recombinant inbred (RI) mouse strains. Electrocardiogram data were recorded from 30 strains of inbred mice and 29 RI strains. Significant differences in mean HR and total power (TP) HRV were identified between inbred strains and RI strains. Multiple significant differences within the strain sets in mean low-frequency (LF) and high-frequency (HF) power were also found. No statistically significant concordance was found between strain distribution patterns for HR and HRV phenotypes. Genomewide interval mapping identified a significant quantitative trait locus (QTL) for HR [LOD (likelihood of the odds) score = 3.763] on chromosome 6 [peak at 53.69 megabases (Mb); designated HR 1 (Hr1)]. Suggestive QTLs for TP were found on chromosomes 2, 4, 5, 6, and 14. A suggestive QTL for LF was found on chromosome 16; for HF, we found one significant QTL on chromosome 5 (LOD score = 3.107) [peak at 53.56 Mb; designated HRV-high-frequency 1 (Hrvhf1)] and three suggestive QTLs on chromosomes 2, 11 and 15. In conclusion, the results demonstrate a strong genetic component in the regulation of resting HR and HRV evidenced by the significant differences between strains. A lack of correlation between HR and HRV phenotypes in some inbred strains suggests that different sets of genes control the phenotypes. Furthermore, QTLs were found that will provide important insight to the genetic regulation of HR and HRV at rest.

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References

Voigt B, Kuramoto T, Mashimo T, Tsurumi T, Sasaki Y, Hokao R . Evaluation of LEXF/FXLE rat recombinant inbred strains for genetic dissection of complex traits. Physiol Genomics. 2007; 32(3):335-42. DOI: 10.1152/physiolgenomics.00158.2007. View

Parati G, Di Rienzo M . Determinants of heart rate and heart rate variability. J Hypertens. 2003; 21(3):477-80. DOI: 10.1097/00004872-200303000-00007. View

Hoit B, Kiatchoosakun S, Restivo J, Kirkpatrick D, Olszens K, Shao H . Naturally occurring variation in cardiovascular traits among inbred mouse strains. Genomics. 2002; 79(5):679-85. DOI: 10.1006/geno.2002.6754. View

Brown T, Beightol L, Koh J, Eckberg D . Important influence of respiration on human R-R interval power spectra is largely ignored. J Appl Physiol (1985). 1993; 75(5):2310-7. DOI: 10.1152/jappl.1993.75.5.2310. View

Malliani A . The Pattern of Sympathovagal Balance Explored in the Frequency Domain. News Physiol Sci. 2001; 14:111-117. DOI: 10.1152/physiologyonline.1999.14.3.111. View

Just A, Faulhaber J, Ehmke H . Autonomic cardiovascular control in conscious mice. Am J Physiol Regul Integr Comp Physiol. 2000; 279(6):R2214-21. DOI: 10.1152/ajpregu.2000.279.6.R2214. View

Marks B, Lightfoot J . Reproducibility of resting heart rate variability with short sampling periods. Can J Appl Physiol. 1999; 24(4):337-48. DOI: 10.1139/h99-026. View

Tankersley C, Irizarry R, Flanders S, Rabold R . Circadian rhythm variation in activity, body temperature, and heart rate between C3H/HeJ and C57BL/6J inbred strains. J Appl Physiol (1985). 2002; 92(2):870-7. DOI: 10.1152/japplphysiol.00904.2001. View

Malpas S . Neural influences on cardiovascular variability: possibilities and pitfalls. Am J Physiol Heart Circ Physiol. 2001; 282(1):H6-20. DOI: 10.1152/ajpheart.2002.282.1.H6. View

10.

Tsuji H, Larson M, Venditti Jr F, Manders E, Evans J, Feldman C . Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996; 94(11):2850-5. DOI: 10.1161/01.cir.94.11.2850. View

11.

Conti L, Jirout M, Breen L, Vanella J, Schork N, Printz M . Identification of quantitative trait Loci for anxiety and locomotion phenotypes in rat recombinant inbred strains. Behav Genet. 2004; 34(1):93-103. DOI: 10.1023/B:BEGE.0000009479.02183.1f. View

12.

Stiedl O, Meyer M . Cardiac dynamics in corticotropin-releasing factor receptor subtype-2 deficient mice. Neuropeptides. 2003; 37(1):3-16. DOI: 10.1016/s0143-4179(02)00135-x. View

13.

Wang J, Williams R, Manly K . WebQTL: web-based complex trait analysis. Neuroinformatics. 2004; 1(4):299-308. DOI: 10.1385/NI:1:4:299. View

14.

Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O . Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005; 1(4):259-71. DOI: 10.1016/j.cmet.2005.03.002. View

15.

Barouch L, Cappola T, Harrison R, Crone J, Rodriguez E, Burnett A . Combined loss of neuronal and endothelial nitric oxide synthase causes premature mortality and age-related hypertrophic cardiac remodeling in mice. J Mol Cell Cardiol. 2003; 35(6):637-44. DOI: 10.1016/s0022-2828(03)00079-8. View

16.

Hayano J, Mukai S, Sakakibara M, Okada A, Takata K, FUJINAMI T . Effects of respiratory interval on vagal modulation of heart rate. Am J Physiol. 1994; 267(1 Pt 2):H33-40. DOI: 10.1152/ajpheart.1994.267.1.H33. View

17.

Acharya U R, Kannathal N, Sing O, Ping L, Chua T . Heart rate analysis in normal subjects of various age groups. Biomed Eng Online. 2004; 3(1):24. PMC: 493278. DOI: 10.1186/1475-925X-3-24. View

18.

Tovote P, Meyer M, Beck-Sickinger A, von Horsten S, Ogren S, Spiess J . Central NPY receptor-mediated alteration of heart rate dynamics in mice during expression of fear conditioned to an auditory cue. Regul Pept. 2004; 120(1-3):205-14. DOI: 10.1016/j.regpep.2004.03.011. View

19.

Hollon T, Bek M, Lachowicz J, Ariano M, Mezey E, Ramachandran R . Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci. 2002; 22(24):10801-10. PMC: 6758465. View

20.

Eckberg D . Sympathovagal balance: a critical appraisal. Circulation. 1997; 96(9):3224-32. DOI: 10.1161/01.cir.96.9.3224. View