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

Mineyoshi Hiyoshi, Hirokazu Uemura, Kokichi Arisawa, Mariko Nakamoto, Asahi Hishida, Rieko Okada, Keitaro Matsuo, Yoshikuni Kita, Hideshi Niimura, Nagato Kuriyama, Hinako Nanri, Ohnaka Keizo, Sadao Suzuki, Haruo Mikami, Michiaki Kubo, Hideo Tanaka, Nobuyuki Hamajima

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)97-102
Number of pages6
JournalGene
Volume496
Issue number2
DOIs
Publication statusPublished - Apr 1 2012

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Catechol O-Methyltransferase
Alanine Transaminase
Homozygote
Serum
Liver
Odds Ratio
gamma-Glutamyltransferase
Carbon Tetrachloride
Liver Neoplasms
Heterozygote
Aspartate Aminotransferases
Liver Cirrhosis
Proteomics
Population
Japan
Homeostasis
Cohort Studies
Cross-Sectional Studies
Logistic Models
Genotype

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Hiyoshi, M., Uemura, H., Arisawa, K., Nakamoto, M., Hishida, A., Okada, R., ... Hamajima, N. (2012). Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity. Gene, 496(2), 97-102. https://doi.org/10.1016/j.gene.2012.01.015

Association between the catechol-O-methyltransferase (rs4680 : Val158Met) polymorphism and serum alanine aminotransferase activity. / Hiyoshi, Mineyoshi; Uemura, Hirokazu; Arisawa, Kokichi; Nakamoto, Mariko; Hishida, Asahi; Okada, Rieko; Matsuo, Keitaro; Kita, Yoshikuni; Niimura, Hideshi; Kuriyama, Nagato; Nanri, Hinako; Keizo, Ohnaka; Suzuki, Sadao; Mikami, Haruo; Kubo, Michiaki; Tanaka, Hideo; Hamajima, Nobuyuki.

In: Gene, Vol. 496, No. 2, 01.04.2012, p. 97-102.

Research output: Contribution to journalArticle

Hiyoshi, M, Uemura, H, Arisawa, K, Nakamoto, M, Hishida, A, Okada, R, Matsuo, K, Kita, Y, Niimura, H, Kuriyama, N, Nanri, H, Keizo, O, Suzuki, S, Mikami, H, Kubo, M, Tanaka, H & Hamajima, N 2012, 'Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity', Gene, vol. 496, no. 2, pp. 97-102. https://doi.org/10.1016/j.gene.2012.01.015
Hiyoshi, Mineyoshi ; Uemura, Hirokazu ; Arisawa, Kokichi ; Nakamoto, Mariko ; Hishida, Asahi ; Okada, Rieko ; Matsuo, Keitaro ; Kita, Yoshikuni ; Niimura, Hideshi ; Kuriyama, Nagato ; Nanri, Hinako ; Keizo, Ohnaka ; Suzuki, Sadao ; Mikami, Haruo ; Kubo, Michiaki ; Tanaka, Hideo ; Hamajima, Nobuyuki. / Association between the catechol-O-methyltransferase (rs4680 : Val158Met) polymorphism and serum alanine aminotransferase activity. In: Gene. 2012 ; Vol. 496, No. 2. pp. 97-102.
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AU - Hiyoshi, Mineyoshi

AU - Uemura, Hirokazu

AU - Arisawa, Kokichi

AU - Nakamoto, Mariko

AU - Hishida, Asahi

AU - Okada, Rieko

AU - Matsuo, Keitaro

AU - Kita, Yoshikuni

AU - Niimura, Hideshi

AU - Kuriyama, Nagato

AU - Nanri, Hinako

AU - Keizo, Ohnaka

AU - Suzuki, Sadao

AU - Mikami, Haruo

AU - Kubo, Michiaki

AU - Tanaka, Hideo

AU - Hamajima, Nobuyuki

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N2 - 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.

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