Association of β-adrenoceptor polymorphisms with cardiac autonomic modulation in Japanese males
Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan. American heart journal
(Impact Factor: 4.46).
10/2007; 154(4):759-66. DOI: 10.1016/j.ahj.2007.03.053
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.
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.
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.
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.
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