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1. Drug Metab Pharmacokinet. 2012 Mar 6. [Epub ahead of print]

Effects of UGT1A6, UGT2B7, and CYP2C9 genotypes on plasma concentrations of
valproic acid in Chinese children with epilepsy.

Guo Y, Hu C, He X, Qiu F, Zhao L.

The State Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin
University.

Valproic acid (VPA) is one of the most commonly prescribed drugs for the
treatment of epilepsy. Interindividual variability in VPA dose and plasma
concentration may reflect functional consequences of genetic polymorphisms in
genes encoding drug-metabolizing enzymes.The aim of this study was to determine
the relationship between plasma concentrations of VPA and single nucleotide
polymorphisms (SNPs) involving uridine diphosphate glucuronosyltransferase (UGT)
1A6 (UGT1A6), UGT2B7, and cytochrome P450 2C9 (CYP2C9) genes in Chinese children
with epilepsy. UGT1A6, UGT2B7, and CYP2C9 polymorphisms were identified by
polymerase chain reaction-restriction fragment length polymorphism approach or
direct automated DNA sequencing in 98 epileptic patients treated with VPA
monotherapy. Patients with double heterozygosities at nucleotide positions T19G,
A541G and A552C in the UGT1A6 gene, were associated with higher VPA doses
compared to those with wild type or single heterozygosity (P=0.010). Lower
adjusted plasma VPA concentrations were also observed in patients with UGT1A6
double heterozygosities than those with single heterozygosity (p=0.027). There
were no differences in VPA dose or adjusted plasma VPA concentrations among the
UGT2B7*2 or CYP2C9*3 genotypic groups. These results suggest that UGT1A6
mutations affect VPA metabolism in epileptic children. It needs to be further
investigated in a larger cohort of patients.

PMID: 22447114 [PubMed - as supplied by publisher]