Clustering heart rate dynamics is associated with β-adrenergic receptor polymorphisms: analysis by information-based similarity index.

• Main Authors: Albert C Yang, Shih-Jen Tsai, Chen-Jee Hong, Cynthia Wang, Tai-Jui Chen, Ying-Jay Liou, Chung-Kang Peng
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2011-05-01
• Series: PLoS ONE
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21573230/?tool=EBI

<h4>Background</h4>Genetic polymorphisms in the gene encoding the β-adrenergic receptors (β-AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype-phenotype analysis to investigate the association between β-AR gene polymorphisms and heart rate dynamics.<h4>Methods</h4>A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6 ± 10.8 years, range 19 to 63 years) were recruited and genotyped for three common β-AR polymorphisms: β(1)-AR Ser49Gly, β(2)-AR Arg16Gly and β(2)-AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects.<h4>Results</h4>With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of β(2)-AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity.<h4>Conclusions</h4>We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with β-AR polymorphisms. Our results provide evidence that β(2)-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control.