Analysis of heart rate variability (HRV) has been proposed to be a quantitative phenotypic marker of autonomic nervous system activity. The evidences of the association between HRV and genetic polymorphisms are limited. We have identified two neuropsychiatry-related genes that are associated with changes in HRV measures: apolipoprotein E (APOE) gene  and brain-derived neurotrophic factor (BDNF) gene .
Apolipoprotein E gene and heart rate complexity
Aging and illness have been suggested to be associated with reduced behavioral or physiological complexity . Little is known about the genetic predisposition to reduced physiological complexity among the elderly. We applied the MSE analysis (as shown in nonlinear HRV methods) to examine effects of the APOE genotypes on heart rate complexity in a cohort of robust elderly adults . Our results show that the reduced physiological complexity is associated with the APOE ε4 allele in this elderly sample, suggesting a pivotal role of genetic inference in physiological aging and autonomic dysregulation. Therefore, further research is warranted to examine if an appropriate treatment/prevention can compensate the adverse impact of APOE ε4 allele on physiological functions.
Brain-derived neurotrophic factor gene and sympathovagal balance
BDNF, a secretory protein in the neurotrophin family, is essential for the survival, development and maintenance of the neuronal system. A functional Val66Met polymorphism in the human BDNF gene has been found in studies of both humans and animals to affect anxiety traits and behaviors and that it may also have neurotrophic or regulatory effects in neurons related to both the sympathetic and parasympathetic systems. We studied the association between BDNF Val66Met polymorphism and time/frequency components of HRV in healthy subjects . We found that subjects bearing the BDNF Met/Met genotype had decreased RMSSD, pNN50, and high-frequency power and increased low-frequency/high-frequency ratio. Those study findings suggest an altered sympathovagal balance with reduced parasympathetic modulation and possibly increased sympathetic activity. This observation leads to further investigation of BDNF-associated ANS imbalance on incidence of anxiety disorders and cardiovascular diseases.
1. Cheng D, Tsai SJ, Hong CJ, Yang AC. Reduced physiologic complexity of heart rate dynamics in healthy elderly men with APOE ε4 allele. PLoS ONE 4(11):e7733 (2009). [PDF]
2. Yang AC, Chen TJ, Tsai SJ, Hong CJ, Kuo CH, Yang CH, Kao KP.* BDNF Val66Met polymorphism alters sympathovagal balance in healthy subjects. American Journal of Medical Genetics B 153B(5):1024-30 (2010). [PDF]
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