title: Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity.
abstract: In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L ≤; males n=239, females n=90) and normal (<30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11-0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function.
authors.affiliation: Department of Preventive Medicine, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan. hiyoshi@basic.med.tokushima-u.ac.jp
authors.forename: Mineyoshi
authors.initials: M
authors.lastname: Hiyoshi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Uemura
authors.forename: Kokichi
authors.initials: K
authors.lastname: Arisawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakamoto
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Kita
authors.forename: Hideshi
authors.initials: H
authors.lastname: Niimura
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.forename: Hinako
authors.initials: H
authors.lastname: Nanri
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D040901:Proteomics / Q000379:methods
chemical_list: D002394:Catechol O-Methyltransferase; D000410:Alanine Transaminase