Influence of <i>UGT2B7</i> and <i>UGT1A6</i> polymorphisms on plasma concentration to dose ratio of valproic acid in Chinese epileptic children
Creators: name: Du, Zhaosong
name: Xu, Hua
name: Zhao, Peiwei
name: Wang, Jing
name: Xu, Qiong
name: Liu, Maochang
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biochemistry
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Neuroscience
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Mental Health
subject: Hematology

description: We explored the potential effects of genetic variations on the concentration to dose ratio (CDR) of valproic acid (VPA) in paediatric epilepsy patients.Two hundred and twenty-nine epileptic children on VPA monotherapy were included, and the VPA trough concentrations at steady-state of all subjects were determined.Nineteen single nucleotide polymorphisms (SNPs) of seven selected genes related to the metabolising enzymes and transporters of VPA were identified, and their influences on CDR<sub>VPA</sub> (a logarithmic transformation was performed if abnormally distributed) were evaluated.<i>UGT2B7</i> rs7668258 (C&gt;T) TT genotype was associated with a decrease in lnCDR<sub>VPA</sub> among epileptic children receiving VPA monotherapy (<i>β</i>=–0.191, <i>p</i> = 0.036). Significantly lower lnCDR<sub>VPA</sub> was also observed in paediatric patients with <i>UGT1A6</i> rs2070959 (A&gt;G) GG genotype compared to those AA genotype (<i>β</i>=–0.270, <i>p</i> = 0.021).This research indicated that <i>UGT2B7</i> rs7668258 (C&gt;T) and <i>UGT1A6</i> rs2070959 (A&gt;G) polymorphisms may be correlated to the normalised plasma concentrations of VPA in Chinese epileptic children. The associations could be abolished after Bonferroni's correction and our findings need to be validated in further and larger investigations. We explored the potential effects of genetic variations on the concentration to dose ratio (CDR) of valproic acid (VPA) in paediatric epilepsy patients. Two hundred and twenty-nine epileptic children on VPA monotherapy were included, and the VPA trough concentrations at steady-state of all subjects were determined. Nineteen single nucleotide polymorphisms (SNPs) of seven selected genes related to the metabolising enzymes and transporters of VPA were identified, and their influences on CDR<sub>VPA</sub> (a logarithmic transformation was performed if abnormally distributed) were evaluated. <i>UGT2B7</i> rs7668258 (C&gt;T) TT genotype was associated with a decrease in lnCDR<sub>VPA</sub> among epileptic children receiving VPA monotherapy (<i>β</i>=–0.191, <i>p</i> = 0.036). Significantly lower lnCDR<sub>VPA</sub> was also observed in paediatric patients with <i>UGT1A6</i> rs2070959 (A&gt;G) GG genotype compared to those AA genotype (<i>β</i>=–0.270, <i>p</i> = 0.021). This research indicated that <i>UGT2B7</i> rs7668258 (C&gt;T) and <i>UGT1A6</i> rs2070959 (A&gt;G) polymorphisms may be correlated to the normalised plasma concentrations of VPA in Chinese epileptic children. The associations could be abolished after Bonferroni's correction and our findings need to be validated in further and larger investigations.