Association of V227A PPARα polymorphism with altered serum biochemistry and alcohol drinking in Japanese men

Hisao Naito, Osamu Yamanoshita, Michihiro Kamijima, Takahiko Katoh, Tadashi Matsunaga, Chul Ho Lee, Heon Kim, Toshifumi Aoyama, Frank J. Gonzalez, Tamie Nakajima

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19 Citations (Scopus)

Abstract

OBJECTIVES: Peroxisome proliferator-activated receptor (PPAR) α plays a major role in alcoholic liver disease in rodents. The two-fold objective of our study was to determine the presence of PPARα 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 PPARα was performed in 706 Japanese men; from these subjects 655 men were further studied after exclusion criteria were applied. RESULTS: PPARα-V227A, which has not been reported in Europe and North America as a major polymorphism, was discovered with the frequency of 0.05. PPARα-L162V was found in European and North American populations, but not in Japanese, thus confirming the ethnic differences in PPARα 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 PPARα-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 PPARα-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. CONCLUSION: PPARα-V227A is a major polymorphism in the Japanese population, and its activity may be greater compared to wild-type, but decreased by alcohol drinking.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalPharmacogenetics and Genomics
Volume16
Issue number8
DOIs
Publication statusPublished - 2006 Aug
Externally publishedYes

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Keywords

  • Alcoholic liver disease
  • ALDH2
  • Cholesterol
  • Molecular epidemiology
  • Peroxisome proliferator-activated receptor α
  • Polymorphism
  • SNP

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Naito, H., Yamanoshita, O., Kamijima, M., Katoh, T., Matsunaga, T., Lee, C. H., Kim, H., Aoyama, T., Gonzalez, F. J., & Nakajima, T. (2006). Association of V227A PPARα polymorphism with altered serum biochemistry and alcohol drinking in Japanese men. Pharmacogenetics and Genomics, 16(8), 569-577. https://doi.org/10.1097/01.fpc.0000220565.90466.79