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


METHODS
One hundred forty-nine young healthy Japanese males were genotyped for each RAS polymorphism.


METHODS
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.
Nishikino
Mariko
M
Department of Endocrinology, Metabolism, and Diabetes Mellitus, Kinki University School of Medicine, Osaka-Sayama 589-8511, Japan.
Matsunaga
Tetsuro
T
Yasuda
Koichiro
K
Adachi
Tetsuya
T
Moritani
Toshio
T
Tsujimoto
Gozoh
G
Tsuda
Kinsuke
K
Aoki
Norihiko
N
D000293:Adolescent; D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D044466:Asian People; D001341:Autonomic Nervous System / Q000502:physiology*; D005787:Gene Frequency; D014644:Genetic Variation; D006262:Health; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A