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The correlation between GSTP1 rs1695、CAT rs769217 and valproate-induced AST elevation in Chinese epilepsy children
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  • Linlin Wang,
  • Lihong Shi,
  • Guangtiing Zeng,
  • Miaomiao Zhu ,
  • Huilan Li ,
  • Jia Luo,
  • zanling zhang
Linlin Wang
Department of Pharmacy, Xiangya Hospital, Central South University,Changsha, Hunan, China
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Lihong Shi
Department of Pharmacy, Xiangya Hospital, Central South University,Changsha, Hunan, China
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Guangtiing Zeng
Department of Pharmacy, Xiangya Hospital, Central South University,Changsha, Hunan, China
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Miaomiao Zhu
Tongji Medical College, Huazhong University of Science and Technology; Wuhan Mental Health Centre; Wuhan Hospital for Psychotherapy,Wuhan, Hubei, China
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Huilan Li
Department of Pharmacy, Xiangya Hospital, Central South University,Changsha, Hunan, China
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Jia Luo
Department of Pharmacy, Xiangya Hospital, Central South University,Changsha, Hunan, China
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zanling zhang
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Abstract

Aims: Children are high risk groups of valproate (VPA) mediated hepatotoxicity, and oxidative stress plays an important role in the process. This study aimed to determine the association between key genetic polymorphisms of antioxidant pathway GSTP1 rs1695, PON1 rs662, CAT rs769217 and VPA mediated abnormal AST elevation. Methods: A total of 194 eligible children with newly diagnosed epilepsy who aged 1 to 16 years old were selected and treated with valproate. According to the AST abnormalities at the maximum AST during the treatment, the subjects were divided into AST normal group and AST elevation group. SNPscan was used for genotyping. Results: In this study, 25.8% of the patients had AST elevation during VPA treatment. The maximum value of AST in patients with AA genotype of GSTP1 rs1695 during VPA monotherapy was significantly higher than that of patients carrying G alleles (36.50 ±14.89 vs 32.88±10.69, P=0.003). The maximum value of AST in CAT rs769217 genotypes were significantly different (P=0.011, P= 0.045, respectively). The risk of GSTP1 rs1695 AG+GG genotype of AST elevation was reduced (adjusted OR=0.37, 95% CI:0.16-0.84, P=0.017). And the risk of CAT rs769217 CT genotype or CT+TT genotype of AST elevation was reduced (adjusted OR=0.30, 95% CI:0.13-0.68, P=0.004 and adjusted OR=0.41, 95% CI:0.20-0.82,P=0.012, respectively). Conclusion: GSTP1 rs1695 and CAT rs769217 are related to VPA-induced AST abnormalities in children. Carriers of GSTP1 rs1695 G allele have a reduced risk of AST abnormalities. CAT rs769217 CC genotype is a risk factor for abnormal AST.

Peer review status:POSTED

15 Sep 2020Submitted to British Journal of Clinical Pharmacology
16 Sep 2020Assigned to Editor
16 Sep 2020Submission Checks Completed