The correlation between GSTP1 rs1695、CAT rs769217 and valproate-induced
AST elevation in Chinese epilepsy children
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.