EFfects of UGT1A, CYP2C9/19 and ABAT Polymorphisms on Plasma Concentration of Valproic Acid in Chinese Epilepsy Patients

Abstract

Aim: To evaluate the association between genetic polymorphisms and plasma concentration-to-dose ratio of valproic acid (CDRV) in Chinese epileptic patients. Methods: A total of 46 epileptic patients treated with valproic acid therapy were enrolled. 18 SNPs in nine genes related to valproic acid were directly sequenced with Sanger methods. Results: Patients carrying UGT1A6 heterozygous genotypes had significantly lower CDRV than those carrying the wild-type genotypes. In contrast, patients with the homozygote genotypes of CYP2C9 and ABAT had higher CDRV than those with the wild-type genotypes and patients with the heterozygous genotypes of CYP2C19 had higher CDRV. Conclusion: Detection of genetic polymorphism in these genes might facilitate an appropriate dose of valproic acid for epileptic patients. Further studies with larger cohorts are necessary to underpin these observations.

Keywords::

• epilepsy
• genetic polymorphisms
• individual therapy
• plasma concentrations
• valproic acid

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pgs-2022-0156

Author contributions

D Tang, S Xu and X Zheng were responsible for the study design. X Zheng and S Xu were responsible for recruiting subjects. X Zheng, S Xu, D Tang and Y Du were responsible for collecting clinical data and performing the clinical ratings. Y You, L Zhao and X Zheng were responsible for statistical analysis and manuscript preparation. All authors contributed to and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by a grant from the Jiangsu Research Hospital Association for Precision Medication (JY202028) and the Natural Science Foundation of Jiangsu Province of China (no. BK20181147 and BE2019640).The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The protocol of the current study was approved by the Ethics Committee of Xuzhou First People’s Hospital (no. xyy11[2021]32), and all patients who participated in this study provided written informed consent. All methods were carried out according to the relevant guidelines and regulations.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.

Additional information

Funding

This work was supported by a grant from the Jiangsu Research Hospital Association for Precision Medication (JY202028) and the Natural Science Foundation of Jiangsu Province of China (no. BK20181147 and BE2019640).The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. No writing assistance was utilized in the production of this manuscript.