アクティブボード・２００９年１１月
　　　　　・・・・・２００９年１１月　５日更新・・・・・

研究発表を行った学会；
・The International Symposium on Pharmacogenomics in Epilepsy
　２００９年１０月２４日（弘前）

タイトル；Association between mitochondrial superoxide dismutase genotype and serum transaminase levels in patients treated with valproic acid.
　
発表者；　出口　真理子　氏
　　　（熊本大学　大学院医学薬学研究部　薬物治療学分野）

Abstract；
Aim: Mitochondrial dysfunction has been implicated in the pathogenesis of valproic acid (VPA)-induced hepatotoxicity. This study aimed to determine whether a functional polymorphism in mitochondrial superoxide dismutase (SOD2) gene (Val-9Ala, rs4880) could contribute to liver dysfunction in patients treated with VPA.
Methods: The association between the SOD2 genotype and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) was retrospectively investigated in 208 epileptic patients (127 males, 0.4-74 yr).
Results: The SOD2 Val allele frequency was 88.2%, and the genotype distribution was in Hardy-Weinberg equilibrium. The serum ALT, AST and GGT levels were higher in the Val/Val genotype than in the other genotypes; median, 20 (range, 4-317) IU/l vs. 17 (8-80) IU/l, P=0.081; 26 (11-285) IU/l vs. 23 (12-50) IU/l, P=0.034; and 28 (8-944) IU/l vs. 19 (6-623) IU/l, P=0.051; respectively. The incidences of cases over the upper limit of normal were higher also in the Val/Val genotype than in the other genotypes; in ALT, 20.9% vs. 6.7%, with odds ratio (OR) of 3.7 [95% confidence interval (CI) 1.08-12.6]; in AST, 17.8% vs. 11.1%, with OR of 1.7 (95% CI 0.63-4.77) and in GGT, 51.2% vs. 31.0%, with OR of 2.3 (95% CI 1.14-4.83).
Conclusion: The SOD2 Val/Val genotype may be a novel genetic risk factor for VPA-induced liver dysfunction in Japanese.