A meta-analysis of the influence of UGT1A6 genetic polymorphisms on valproic acid pharmacokinetics

Objectives: Genetic polymorphisms in UGT1A6 might contribute to interindividual variability in the pharmacokinetics of valproic acid (VPA). However, whether the 541A>G and 552A>C variants decrease VPA concentration remains controversial. Herein, we performed a meta-analysis to evaluate the influence of UGT1A6 genetic polymorphisms on VPA pharmacokinetics. Materials and methods: Searches, two-step selection, data extraction, and quality assessment were performed using a conventional protocol, and the influence of UGT1A6 genetic polymorphisms on concentration-to-dose ratio was quantitatively assessed by pooled analysis using the Comprehensive Meta-Analysis program. Results: Six studies using monotherapy were included in the quantitative analysis. Concentration-to-dose ratio of 541A>G and 552A>C homozygous variant were significantly lower than that of the wild-type (WT; standardized difference in means (SDM) = –0.771, 95% confidence interval (CI) = –1.123 to –0.419; SDM = –0.879, 95% CI = –1.257 to –0.500, respectively). Differences were also significant in both child and adult subgroups analysis. For heterozygous variants, there was no significant difference in concentration-to-dose ratio between 541A>G and 552A>C heterozygous variant and WT (SDM = –0.183, 95% CI = –0.449 to 0.084; SDM = –0.275, 95% CI = –0.647 to 0.097, respectively). Conclusion: In conclusion, concentration-to-dose ratio for VPA monotherapy were significantly lower for UGT1A6 homozygous variants 541A>G and 552A>C than for the WT.