Association of beta-adrenoceptor polymorphisms with cardiac autonomic modulation in Japanese males.
BACKGROUND
The beta1- and beta2-adrenergic receptors (ARs) coexist in the human heart and control sympathetic responses. Several functional genetic variations in the beta-AR genes (ADRB1 or ADRB2) have been identified and implicated as causes of hypertension and cardiovascular disease. We assessed the relationship between 4 representative genetic polymorphisms of beta-AR (Ser49Gly and Arg389Gly in beta1-AR, Arg16Gly and Gln27Glu in beta2-AR) and autonomic nervous system (ANS) function in healthy young Japanese males.


METHODS
One hundred forty-nine subjects were genotyped for each beta-AR polymorphism and underwent evaluation of ANS function by power spectral analysis of heart rate variability (HRV) during supine rest and in a standing position. The low-frequency (LF; <0.15 Hz) and high-frequency (HF; >0.15 Hz) components of HRV were quantified by frequency domain analysis and expressed in absolute and normalized units.


RESULTS
The beta2-AR Arg16 homozygous group had a significantly lower diastolic and mean blood pressure than the Gly16 group in both Arg16Gly individual and Gln27Glu polymorphism combined diplotype-based analyses. In a supine rest position, subjects homozygous for the beta2-AR Arg16 allele had significantly lower HRV sympathetic indices (LF [%] and LF/HF ratio) but higher HRV parasympathetic indices (HF [%]) than the Gly16 allele carriers. Meanwhile, the beta2-AR Glu27 allele was significantly associated with higher HRV LF power than were Gln27 homozygous subjects. In the analysis of gene-gene interaction, the effects of the beta2-AR Arg16 homozygotes on HRV were more apparent in the presence of the beta1-AR Gly389 allele. No independent associations were observed between the beta1-AR Ser49Gly or Arg389Gly genotypes and HRV indices.


CONCLUSIONS
The Arg16Gly polymorphism of the beta2-AR is related to the modulation of sympathovagal balance, and beta2-AR Glu27 allele carriers potentially have increased autonomic activity. Thus, beta-AR genotype-related differences in basic receptor function cause phenotypic differences in cardiac ANS function.
Matsunaga
Tetsuro
T
Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
Yasuda
Koichiro
K
Adachi
Tetsuya
T
Gu
Ning
N
Yamamura
Tsubasa
T
Moritani
Toshio
T
Tsujimoto
Gozoh
G
Tsuda
Kinsuke
K
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001341:Autonomic Nervous System / Q000502:physiology*; D004562:Electrocardiography; D005787:Gene Frequency; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic / Q000502:physiology*; D011187:Posture / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013564:Sympathetic Nervous System / Q000502:physiology
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D001120:Arginine; D005998:Glycine