Association of beta-adrenoceptor polymorphisms with cardiac autonomic modulation in Japanese males.
ABSTRACT 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.
- SourceAvailable from: Grazia Guerra
- "In a published study conducted with young Japanese male subjects, homozygous carriers of the β 2 -AR Arg16 allele had lower sympathetic activity than subjects with the Gly allele, and carriers of β 2 -AR Glu27 allele were linked with higher cardiac sympathetic autonomic activity . However, given the significant differences in genetic profile of different racial/ethnic groups, we carried out a study to test the hypothesis that Arg16Gly and Gln27Glu β 2 -AR polymorphisms influence functional physiological characteristics, such as HR, cardiac sympathetic modulation, and CV reflex control, which are considered intermediate phenotypes with profound implications for the development of CV disease. "
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- "In a published study conducted with young Japanese male subjects, homozygous carriers of the β2-AR Arg16 allele had lower sympathetic activity than subjects with the Gly allele, and carriers of β2-AR Glu27 allele were linked with higher cardiac sympathetic autonomic activity . However, given the significant differences in genetic profile of different racial/ethnic groups, we carried out a study to test the hypothesis that Arg16Gly and Gln27Glu β2-AR polymorphisms influence functional physiological characteristics, such as HR, cardiac sympathetic modulation, and CV reflex control, which are considered intermediate phenotypes with profound implications for the development of CV disease. "
ABSTRACT: The association between functional β2 adrenergic receptor (β2-AR) polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common polymorphisms in the β2-AR gene (Gln27Glu β2 and Arg16Gly β2) were studied to determine whether they might affect tonic and reflex cardiac sympathetic activity in healthy young subjects. A total of 213 healthy young white subjects of both genders (53% female), aged 18-30 years (23.5±3.4 y), had their continuous blood pressure curves noninvasively recorded by Finometer at baseline, and other hemodynamic parameters, as cardiac autonomic modulation, baroreflex sensitivity, and allele, genotype, and diplotype frequencies calculated. Associations were made between Arg16Gly β2 and Gln27Glu β2 polymorphisms and between β2-AR diplotypes and all variables. The heart rate was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles (60.9±1.5 bpm) than in that of Arg/Gly heterozygotes (65.9±1.0 bpm) or Gly/Gly homozygotes (66.3±1.2 bpm). Homozygous carriers of Arg16 allele had an alpha index (19.2±1.3) significantly higher (P<0.001) than that of the subjects with the Gly allele Gly/Gly (14.5±0.7) or Arg/Gly (14.6±0.7). Furthermore, the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1% vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the presence of β2-AR Arg16 allele in a recessive model was associated with higher baroreflex sensitivity, and increased parasympathetic modulation in studied individuals.American Journal of Translational Research 03/2015; 7(1):153-61. · 3.40 Impact Factor
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- "This may indicate either that the magnitude of genetic influences is reduced or that the number of genes that influence RSA is small. Several candidate genes have been identified for RSA, including the b2-adrenergic receptor gene (Matsunaga et al., 2007), the estrogen receptor a gene (Matsunaga et al., 2010), the angiotensin converting enzyme gene (Thayer et al., 2003), and the epidermal growth factor gene (Puttonen et al., 2005). However, functional polymorphisms in other physiologically relevant genes failed to show an association with RSA: several genes related to the renin-angiotensin system (Nishikino et al., 2006), the choline transporter gene (Neumann, Lawrence, This study was supported by Grant 27020/35/15.11.2011 from " I. Hat¸ieganu " University of Medicine and Pharmacy to the first author. "
ABSTRACT: It has been recently reported in Psychophysiology that carriers of the short allele of an insertion/deletion (ins/del) functional polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene may display decreased resting respiratory sinus arrhythmia (RSA). However, this region hosts another functionally connected single-nucleotide polymorphism (rs25531), which should also be genotyped in order to correctly categorize the low- and high-expressing alleles of 5-HTTLPR. The present study investigated resting RSA in an ethnically homogenous sample (N = 143) of participants genotyped for both the ins/del and rs25531 polymorphisms in 5-HTTLPR. In contrast with the biallelic genotypes, based only on the ins/del alleles, the triallelic 5-HTTLPR genotypes (i.e., including rs25531) showed no association with resting RSA. Taking a triallelic approach to 5-HTTLPR is thus necessary in order to avoid false positive results.Psychophysiology 08/2012; 49(10):1412-6. DOI:10.1111/j.1469-8986.2012.01445.x · 3.18 Impact Factor