Effects of functional polymorphisms related to catecholaminergic systems on changes in blood catecholamine and cardiovascular measures after alcohol ingestion in the Japanese population.
BACKGROUND
The polymorphism of human aldehyde dehyrogenase-2 (ALDH2) Glu(487)Lys is well known to be a crucial factor underlying the genetic background for alcohol sensitivity in Asian populations. Subjects with the inactive Lys(487) allele show a marked increase in blood acetaldehyde level after alcohol intake, which results in facial flushing and various cardiovascular-related symptoms. However, other polymorphisms related to catecholaminergic systems that tightly regulate the activity of the sympathetic nervous system may also influence the physiological changes after acute alcohol intake.


METHODS
We investigated whether, together with the ALDH2 Gly(487)Lys and ADH1B Arg(47)His genotype, putative functionally important polymorphisms, including 9 loci in 7 human genes, were associated with changes in blood catecholamine levels and cardiovascular measures after alcohol ingestion. Forty-nine young Japanese males were subjected to blood catecholamine analysis after alcohol ingestion. Among them, 28 were also subjected to heart rate variability and blood pressure analysis. The contribution of polymorphisms to the alcohol-induced response was analyzed by multiple regression analysis.


RESULTS
Among the polymorphisms examined in this study, haplotypes of the phenylethanolamine N-methyltransferase (PNMT) promoter [(-182bpG/A)_(-387bpG/A)] and catechol-O-methyltransferase (COMT) exon 4 [(Ex4 + 119bpC/G)_(Ex4 + 138bpG/A), Leu(136)Leu_Val(158)Met] are suggested to have functionally important effects on alcohol-induced cardiovascular symptoms by affecting blood catecholamine levels. The neuropeptide Y (NPY) promoter C-1450T genotype is also suggested to be involved in the individual differences in regulation of catecholamine secretion.


CONCLUSIONS
This study suggested that these common polymorphisms of genes related to catecholaminergic systems, as well as those of the alcohol metabolizing system, are significant for understanding the basis of individual differences in alcohol sensitivity.
Nishimura
Fusae T
FT
Department of Hygiene, Kanazawa University School of Medicine and Graduate School of Medical Sciences, Kanazawa, Japan.
Kimura
Yukiko
Y
Abe
Shuntaro
S
Fukunaga
Tatsushige
T
Minami
Junichi
J
Tanii
Hideji
H
Saijoh
Kiyofumi
K
D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001794:Blood Pressure / Q000235:genetics; D002320:Cardiovascular Physiological Phenomena / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002395:Catecholamines / Q000097:blood* / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012044:Regression Analysis; D013564:Sympathetic Nervous System / Q000503:physiopathology; D055815:Young Adult
D002395:Catecholamines; D009478:Neuropeptide Y; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D010625:Phenylethanolamine N-Methyltransferase; D002394:Catechol O-Methyltransferase