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Genetics of Heart Rate Variability

BY: Hareepriyaw M | Category: Genetics | Submitted: 2013-12-08 02:22:03
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Article Summary: "From the human genetic studies that were conducted in the past decade, the genomic loci that control the variation in HR are identified. Linkage analysis of resting heart rate was carried out in a study consisting of 962 Caucasian participants and 1124 African-American participants..."


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Introduction

Heart Rate (HR) is determined by various mechanisms. The regulation of heart as it grows older occurs by constant and natural depolarization of sino-atrial (SA) cells. The activity of SA pacemaker cells is controlled by autonomic nervous system, respiration, intrinsic cardiac nervous system and baroreflexes. The sympathetic nervous system triggers post ganglionic sympathetic nerve fibers and norepinephrine release in the SA node, resulting in the increase of Heart Rate . The parasympathetic nervous system has a vital role in the regulation of Heart Rate . The vagal nerve endings of parasympathetic system release acetylcholine which attaches to the cholinergic receptors of pacemaker cells. This event will open the potassium channels and causes hyper polarization of the membrane followed by a decrease in the Heart Rate .

The variability of Heart Rate is affected by mechanical and humoral signals. The mechanoreceptors in the atrium will retort to the movements due to respiration, leading to Heart Rate change without any neural intervention. The baroreceptor reflexes created by changes in blood pressure will also show the impact on Heart Rate . If the blood pressure is high, the carotid sinus and aortic arch receptors that can sense the stretch, will convey action potentials through the vagus nerves and glossopharyngeal nerves to the solitary tract nucleus (NTS) of the brain stem. The NTS triggers the PNS after inhibiting the sympathetic drive by affecting the ventrolateral medulla. This will lead to the reduction in Heart Rate and blood pressure.

Genetics of Heart Rate trait in humans

From the human genetic studies that were conducted in the past decade, the genomic loci that control the variation in Heart Rate are identified. Linkage analysis of resting Heart Rate was carried out in a study consisting of 962 Caucasian participants and 1124 African-American participants. The important locus was identified in chromosome 4 at 195.06 cM. The Heart Rate locus on Chr. 4 had logarithm of Odds ratio score (LOD) as 3.18 for both Caucasians and African-American groups. The same above study also revealed that a locus present on chromosome 10 also contribute to HR.

Another study with 3282 participants of Caucasian and African-American origin revealed two loci. In a Caucasian group called HyperGen, a vital locus on chromosome 10 is found to be linked to HR. The LOD score of this locus was calculated as 4.6 located at 142.78 cM. The region that is common to both the races on chromosome 5p13-14 at LOD of 1.9, showed the impact on HR. The linkage for HR, genome wide was first observed on chromosome 18 with a LOD score of 2.03 and at distance of 77cM among 73 Mongolian families. The second peak with a LOD score of 1.52 was found to be present on chromosome 5 at 216 cM. These results further confirm that the genes responsible for Heart Rate regulation are undoubtedly present on chromosome 5.

Another analysis of three different European groups comprising of 2325 people showed that a locus important for Heart Rate was found to be present on chromosome 12. A specific quantitative trait locus for Heart Rate was found to be present on chromosome 9p21 showing the LOD score at 4.8, in a study called Strong Heart Family Study. Linkage analysis was carried out by the researchers in this study to measure Heart Rate using electrocardiogram and echo-cardiograph Doppler recording, in this population.

Many studies dealing with genome wide linkage evaluated that genetic factors are involved mostly in exercise Heart Rate compared to the training HR. The HERITAGE family study could detect the genetic loci present in 99 white families and 127 black families. The genetic loci that are associated with resting Heart Rate were found to be different in both the races. White families had these gene loci present in the chromosomes 4 and 11. Black families had these loci on chromosomes 2, 6, 7, 12, 14 and 15. The genetic loci associated with training Heart Rate were found to be present on chromosomes 1 and 21 of white families and in chromosomes 3, 20 and 21 of black families.

The follow up study to the above investigation could identify two single nucleotide polymorphisms (SNPs) in the 5' region of the gene named as c AMP responsive element binding protein-1 (CREB1) on the chromosome 2. The same research group identified SNPs in nine other genes indicating that these genes represent the hereditary nature of the training Heart Rate genes. These genes are known to regulate the functions of neuronal cell, formation of cardiac memory and functions of cardiomyocyte. These genes also indicate a heritable feature of the response shown by training HR.

Recent analysis of 15 genome-wide association studies on variation in Heart Rate identified six new loci related to resting HR. These loci are named as 6q22, 14q12, 12p12, 6q22, 7q22 and 11q12. Locus 6q22 is found to be vital in electrical coupling of myocytes. Gene locus associated with atrial septal defects, hypertrophic cardiomyopathy and dilated cardiomyopathy is 14q12. The locus 12p12 was not associated with the pathophysiology of cardiac diseases. A gene in the locus 7q22 codes for cation-chloride co-transporter interacting protein.



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[b]Reference:[/b]

Vyacheslav A. Korshunov, Igor A. Dyachenko and Arkady N. Murashev. (2013). Genetic Determinants of Heart Rate Variation and Cardiovascular Diseases, Genetic Disorders, Prof. Maria Puiu (Ed.,), ISBN : 978-53-51-0886-3, InTech, DOI:10.5772/53642. Available from: http://www.intechopen.com/books/genetic-disorders/genetic-determinants-of-heart-rate-variation-and-cardiovascular-diseases.


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Comments on this article: (1 comments so far)

Comment By Comment
kumar
2014-01-02 09:57:05 742
Does excess administration of antibiotics through intravenous route cause abnormal increase in heart rate and atrial fibrillation? If so, what is the mechanism that causes it? Can it cause permanent damage to the heart?

Leave a Comment   |   Article Views: 2148



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