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

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.

Molecular mechanisms underlying Warburgia salutaris effects on oxidative stress and apoptotic parameters in Human Hepatoma Cells

“…However, in this study the increase in Nrf2 protein expression did not induce an increase in MnSOD gene expression (Figure 4D and 4.8). In contrast; both GPx (Figure 4E) and catalase (Figure 4C) that function to detoxify H 2 O 2 to H 2 O were increased 33 . Collectively, these results suggest an increase in free radical production and an antioxidant response mounted against it that was inadequate in the prevention of acute oxidative stress.…”

Novel Clinical Biomarkers for Drug-Induced Liver Injury

“…Meanwhile, superoxide dismutase 2 (SOD2) polymorphism was also tested for its potential risk for liver damage, and found that SOD2 Val/Val contributed to VPA-induced liver dysfunction with an elevated γ-glutamyltransferase levels (Saruwataria et al, 2012). Furthermore, catalase (CAT) genotype was reported as a significant genetic risk factor for VPA-induced liver dysfunction, and CAT C-262T carriers exhibited an increased risk of developing abnormal hepatic function compared with the non-carriers (OR=3.968, P = 0.003) (Ma et al, 2019). These findings raise the possibility that GSTs, SOD2 and CAT may be implicated in VPA -induced hepatotoxicity for their roles on the liver oxidative stress.…”

Персонифицированная Гепатопротекция Больных Механической Желтухой Доброкачественного Происхождения

“…Èçìåí÷èâîñòü ãåíîòèïíûõ ñâîéñòâ ãåíîâ àíòèîêñèäàíòíîé ñèñòåìû øèðîêî èçó÷åíà è èññëåäîâàíà ó ïàöèåíòîâ ñ ýíäîêðèííûìè, ñåðäå÷íî-ñîñóäèñòûìè, íåéðîäåãåíåðàòèâíûìè, ãèíåêîëîãè÷åñêèìè, îôòàëüìîëî-ãè÷åñêèìè è äðóãèìè çàáîëåâàíèÿìè. Ïðè ýòîì óñòàíîâëåíà ñîïðÿaeåííîñòü åäèíè÷íûõ ïîëèìîðôèçìîâ íåêîòîðûõ ãåíîâ, êîäèðóþùèõ ïðîäóêöèþ ÑÎÄ, êàòàëàçû è ãëóòàòèîí-S-òðàíñôåðàçû ñ ðèñêîì èõ ðàçâèòèÿ è ïðîãðåññèðîâàíèÿ [14,15,16].…”