Genetic variation in the renin-angiotensin system and autonomic nervous system function in young healthy Japanese subjects.

CONTEXT: The renin-angiotensin system (RAS) interacts with the autonomic nervous system (ANS) in the regulation of blood pressure and cardiovascular function. Several genetic polymorphisms in the RAS have been identified and have been implicated as a cause of hypertension and cardiovascular disease. OBJECTIVE: The aim of the present study was to evaluate the relation between genetic polymorphisms of the RAS (M235T of AGT gene, insertion/deletion of ACE gene, A1166C of AT1R gene, and A1675G of AT2R gene) and ANS function. SUBJECTS: One hundred forty-nine young healthy Japanese males were genotyped for each RAS polymorphism. MAIN OUTCOME MEASURES: ANS function was evaluated by power spectral analysis of heart rate variability (HRV) during supine rest and in a standing position. RESULTS: In a supine position, subjects homozygous for the AGT 235T allele had a higher HRV sympathetic index than 235M allele carriers, whereas the orthostatic change in this index was relatively blunted in AGT 235TT carriers. In the analysis of gene-gene interaction, these effects of the AGT 235T homozygotes on HRV sympathetic index were more apparent in the presence of the ACE D allele. Meanwhile, the AT1R 1166C allele was significantly associated with higher HRV low-frequency power and sympathetic index in a standing position. These data suggest that the AGT M235T polymorphism is associated with sympathetic predominance at rest, and AT1R 1166C allele carriers have potentially increased sympathetic response. CONCLUSIONS: Cardiac autonomic function can be modulated by genetic variation in the RAS even in young and healthy states.

Association of C825T polymorphism of G protein beta3 subunit with the autonomic nervous system in young healthy Japanese individuals.

BACKGROUND: The T allele of the C825T polymorphism of the G protein beta3 subunit gene (GNB3) is reported to be associated with increased intracellular signal transduction and the prevalence of essential hypertension. Because the two major receptors in the autonomic nervous system (ANS), the adrenergic and muscarinic acetylcholine receptors, are G protein-coupled receptors, it was expected that the GNB3 C825T polymorphism was associated with ANS function. In the present study, we have investigated the association of this polymorphism with ANS in young, healthy Japanese male individuals. METHODS: A total of 94 young, healthy subjects underwent the genotyping for the GNB3 C825T polymorphism and electrocardiogram R-R interval power spectral analysis in supine rest and standing positions. RESULTS: There were no significant differences among genotypes in any of the characteristics investigated (body mass index, blood pressure, plasma glucose, insulin, lipids, and family history of hypertension, diabetes, or obesity). However, in power spectral analysis of heart rate variability, the very-low-frequency component when standing was higher in TT carriers than in CC carriers, and TT and CT carriers had a significantly higher sympathetic nervous system (SNS) index and lower parasympathetic nervous system (PNS) index when standing than CC carriers. In addition, we found that TT carriers showed no chronological variations in either SNS or PNS index after postural change. CONCLUSIONS: These observations suggested that GNB3 C825T polymorphism is associated with ANS in youth. These findings raise the possibility that individuals who are T allele carriers are at increased risk for developing hypertension in relation to ANS function.

T393C polymorphism of GNAS1 associated with the autonomic nervous system in young, healthy Japanese subjects.

1. T393C polymorphism of the gene encoding the Gs-protein alpha-subunit (GNAS1) has been reported recently to be associated with hypertension in which dysfunctions of the autonomic nervous system (ANS) are closely involved. In the present study, the association of this polymorphism with ANS activity was investigated in young, healthy Japanese males. 2. Four hundred and one subjects were genotyped for the T393C polymorphism of GNAS1 by polymerase chain reaction-restriction fragment length polymorphism. Autonomic nervous system activity during supine rest and when standing was assessed in 137 subjects by electrocardiogram R-R interval power spectral analysis. 3. One hundred and fifty-four subjects (38.4%) were homozygous for the T allele (TT), 188 (46.9%) were heterozygous (TC) and 59 (14.7%) were homozygous for the C allele (CC). There were no significant differences as to genotype among the clinical characteristics investigated. In power spectral analysis of heart rate variability, the high-frequency component and parasympathetic nervous system (PNS) index during supine rest were significantly lower in TT and TC carriers than in CC carriers. Furthermore, the increase in heart rate and the responsiveness of sympathetic nervous system index and PNS index to postural change from supine rest to standing were significantly lower in TT and TC carriers than in CC carriers. 4. These observations suggest that the GNAS1 T393C polymorphism is associated with ANS activity in youth, so that it may be useful as a genetic marker for future pathogenesis of hypertension. Follow-up studies are necessary to clarify the prevalence rates of hypertension among 393T allele carriers in the present study.