title: Clustering heart rate dynamics is associated with β-adrenergic receptor polymorphisms: analysis by information-based similarity index.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Chu-Tung Veterans Hospital, Hsin-Chu County, Taiwan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yang
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.forename: Chen-Jee
authors.initials: CJ
authors.lastname: Hong
authors.forename: Cynthia
authors.initials: C
authors.lastname: Wang
authors.forename: Tai-Jui
authors.initials: TJ
authors.lastname: Chen
authors.forename: Ying-Jay
authors.initials: YJ
authors.lastname: Liou
authors.forename: Chung-Kang
authors.initials: CK
authors.lastname: Peng
mesh_terms: D000328:Adult; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2