Catalase C-262T Polymorphism Is a Risk Factor for Valproic Acid-Induced Abnormal Liver Function in Chinese Patients With Epilepsy.

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Catalase C-262T Polymorphism Is a Risk Factor for Valproic Acid-Induced Abnormal Liver Function in Chinese Patients With Epilepsy.

Ther Drug Monit. 2019 02;41(1):91-96

Authors: Ma L, Pan Y, Sun M, Shen H, Zhao L, Guo Y

Abstract
BACKGROUND: Individual susceptibility to valproic acid (VPA)-caused hepatotoxicity might result from genetic deficiencies in the detoxification and antioxidant enzymes including glutathione S-transferases (GSTs), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). This study aimed to investigate the relationships between GST mu 1 (GSTM1), GST theta 1 (GSTT1), CAT C-262T, GPx1 Pro200Leu, and SOD2 Val16Ala polymorphisms and the risk of abnormal liver function in Chinese epileptic patients treated with VPA monotherapy.
METHODS: According to the levels of liver function indicators, a total of 267 epileptic patients between 1 and 65 years of age were divided into normal liver function group and abnormal liver function group. GSTM1 and GSTT1 polymorphisms were determined using polymerase chain reaction (PCR) amplification based on the absence of a PCR amplification product. CAT, GPx1, and SOD2 polymorphisms were identified using PCR-restriction fragment length polymorphism or direct automated DNA sequencing.
RESULTS: Carriers of CAT had an increased risk of developing abnormal liver function compared with noncarriers in VPA-treated patients (odds ratio 3.968, P = 0.003). Logistic regression analyses indicated that the CAT genotype was a significant genetic risk factor for VPA-induced liver dysfunction. It suggests that individual susceptibility to VPA-induced liver dysfunction may at least partially result from genetic deficiencies in CAT C-262T.

PMID: 30422963 [PubMed - indexed for MEDLINE]

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