Association of V227A PPARalpha polymorphism with altered serum biochemistry and alcohol drinking in Japanese men.
OBJECTIVE
Peroxisome proliferator-activated receptor (PPAR) alpha plays a major role in alcoholic liver disease in rodents. The two-fold objective of our study was to determine the presence of PPARalpha polymorphisms and their frequencies in Japanese populations and then to evaluate the effects of any alleles on metabolic parameters and alcohol drinking.


METHODS
Analysis of coding SNP in PPARalpha was performed in 706 Japanese men; from these subjects 655 men were further studied after exclusion criteria were applied.


RESULTS
PPARalpha-V227A, which has not been reported in Europe and North America as a major polymorphism, was discovered with the frequency of 0.05. PPARalpha-L162V was found in European and North American populations, but not in Japanese, thus confirming the ethnic differences in PPARalpha allele frequencies. The A227 allele was associated with increased serum concentrations of gamma glutamyltranspeptidase. In non-drinkers, the total cholesterol (TC) levels were significantly lower in those having the PPARalpha-V227A polymorphism. In drinkers, however, it was comparable among V227A polymorphisms, and conversely higher in those having both A227 and aldehyde dehydrogenase 2 (ALDH2) variants when further divided according to the ALDH2 polymorphism. Significant interactions between PPARalpha-V227A polymorphism and drinking were also found for TC, triglyceride levels and AST/ALT ratios. These results suggest that the activity of the A227 allele without drinking may be higher than in wild-type allele, but its activity may become lower during drinking habits.


CONCLUSIONS
PPARalpha-V227A is a major polymorphism in the Japanese population, and its activity may be greater compared to wild-type, but decreased by alcohol drinking.
Naito
Hisao
H
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yamanoshita
Osamu
O
Kamijima
Michihiro
M
Katoh
Takahiko
T
Matsunaga
Tadashi
T
Lee
Chul-Ho
CH
Kim
Heon
H
Aoyama
Toshifumi
T
Gonzalez
Frank J
FJ
Nakajima
Tamie
T
D000428:Alcohol Drinking / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics*; D005787:Gene Frequency; D008040:Genetic Linkage; D006304:Health Status; D006801:Humans; D007564:Japan; D008297:Male; D047493:PPAR alpha / Q000235:genetics*; D011110:Polymorphism, Genetic
D001798:Blood Proteins; D047493:PPAR alpha; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial