Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity

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 (30 IU/L ≤; males n = 239, females n = 90) and normal (< 30 IU/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.

► Previously, we found increase of the COMT phosphorylation in damaged rat liver.
► We hypothesized that the COMT protein is associated with liver function.
► COMT polymorphism that impact on enzymatic activity may affect liver function.
► We used serum alanine aminotransferase (ALT) activity as an index of liver function.
► COMT polymorphism affected serum ALT activity in the general Japanese population.