Effects of UGT1A, CYP2C9/19 and ABAT polymorphisms on plasma concentration of valproic acid in Chinese epilepsy patients

References

• 1. Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol. 15(2), 210–218 (2016).
  Medline CASGoogle Scholar
• 2. Klotz U. The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin. Pharmacokinet. 46(4), 271–279 (2007).
  Medline CASGoogle Scholar
• 3. Romoli M, Mazzocchetti P, D'Alonzo R et al. Valproic acid and epilepsy: from molecular mechanisms to clinical evidences. Curr. Neuropharmacol. 17(10), 926–946 (2019).
  Medline CASGoogle Scholar
• 4. Tan NN, Tang HL, Lin GW et al. Epigenetic downregulation of Scn3a expression by valproate: a possible role in its anticonvulsant activity. Mol. Neurobiol. 54(4), 2831–2842 (2017).
  Medline CASGoogle Scholar
• 5. Wang C, Wang P, Yang LP et al. Association of CYP2C9 , CYP2A6 , ACSM2A , and CPT1A gene polymorphisms with adverse effects of valproic acid in Chinese patients with epilepsy. Epilepsy Res. 132, 64–69 (2017).
  Medline CASGoogle Scholar
• 6. Chatzistefanidis D, Georgiou I, Kyritsis AP et al. Functional impact and prevalence of polymorphisms involved in the hepatic glucuronidation of valproic acid. Pharmacogenomics 13(9), 1055–1071 (2012).
  CASGoogle Scholar
• 7. Banawalikar N, Adiga S, Adiga U et al. Association of UGT1A6 gene polymorphism with clinical outcome in pediatric epileptic patients on sodium valproate monotherapy. Braz. J. Med. Biol. Res. 54(9), e11097 (2021).
  Medline CASGoogle Scholar
• 8. Ghodke-Puranik Y, Thorn CF, Lamba JK et al. Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenet. Genomics 23(4), 236–241 (2013).
  Medline CASGoogle Scholar
• 9. Singh S, Gulati S. Genetic polymorphisms of UDP-glucuronosyltransferases and plasma sodium valproate level. Indian J. Pediatr. 88(8), 747–748 (2021).
  MedlineGoogle Scholar
• 10. Sun YX, Zhuo WY, Lin H et al. The influence of UGT2B7 genotype on valproic acid pharmacokinetics in Chinese epilepsy patients. Epilepsy Res. 114, 78–80 (2015).
  Medline CASGoogle Scholar
• 11. Wolking S, Moreau C, Nies AT et al. Testing association of rare genetic variants with resistance to three common antiseizure medications. Epilepsia 61(4), 657–666 (2020).
  Medline CASGoogle Scholar
• 12. Tan L, Yu JT, Sun YP et al. The influence of cytochrome oxidase CYP2A6 , CYP2B6 , and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients. Clin. Neurol. Neurosurg. 112(4), 320–323 (2010).
  MedlineGoogle Scholar
• 13. Chu XM, Zhang LF, Wang GJ et al. Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients. Eur. J. Clin. Pharmacol. 68(10), 1395–1401 (2012).
  Medline CASGoogle Scholar
• 14. Nandith PB, Adiga U, Shenoy V et al. UGT1A6 and UGT2B7 gene polymorphism and its effect in pediatric epileptic patients on sodium valproate monotherapy. Indian J. Pediatr. 88(8), 764–770 (2021).
  Medline CASGoogle Scholar
• 15. Chatzistefanidis D, Lazaros L, Giaka K et al. UGT1A6- and UGT2B7 -related valproic acid pharmacogenomics according to age groups and total drug concentration levels. Pharmacogenomics 17(8), 827–835 (2016).
  CASGoogle Scholar
• 16. Lu Y, Su Q, Li M et al. Association of SCN1A , SCN2A , and UGT2B7 polymorphisms with responsiveness to valproic acid in the treatment of epilepsy. Biomed. Res. Int. 2020, 8096235 (2020).
  MedlineGoogle Scholar
• 17. Sun Y, Yu J, Yuan Q et al. Early post-traumatic seizures are associated with valproic acid plasma concentrations and UGT1A6/CYP2C9 genetic polymorphisms in patients with severe traumatic brain injury. Scand. J. Trauma Resusc. Emerg. Med. 25(1), 85 (2017).
  MedlineGoogle Scholar
• 18. Zhao M, Chen Y, Wang M et al. Impact of age and genotype on serum concentrations of valproic acid and its hepatotoxic metabolites in Chinese pediatric patients with epilepsy. Ther. Drug Monit. 42(5), 760–765 (2020).
  Medline CASGoogle Scholar
• 19. Ingelman-Sundberg M, Sim SC, Gomez A et al. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol. Ther. 116(3), 496–526 (2007).
  Medline CASGoogle Scholar
• 20. Eltalal S, El Ayouty M, El-Said A et al. CYP2C9 (*2&*3) and CYP2C19 (*2&*3) polymorphisms among children with nonlesional epilepsy: a single-center study. Acta Neurol. Belg. 121(6), 1623–1631 (2021).
  MedlineGoogle Scholar
• 21. Zhao M, Zhang T, Li G et al. Associations of CYP2C9 and CYP2A6 polymorphisms with the concentrations of valproate and its hepatotoxin metabolites and valproate-induced hepatotoxicity. Basic Clin. Pharmacol. Toxicol. 121(2), 138–143 (2017).
  Medline CASGoogle Scholar
• 22. Mani B, Nair PP, Sekhar A et al. CYP2C19 & UGT1A6 genetic polymorphisms and the impact on Valproic acid-induced weight gain in people with epilepsy: prospective genetic association study. Epilepsy Res. 177, 106786 (2021).
  Medline CASGoogle Scholar
• 23. Wang S, Li J, Song M et al. Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia. Sci. Rep. 11(1), 23150 (2021).
  Medline CASGoogle Scholar
• 24. Mei S, Feng W, Zhu L et al. Effect of CYP2C19 , UGT1A8 , and UGT2B7 on valproic acid clearance in children with epilepsy: a population pharmacokinetic model. Eur. J. Clin. Pharmacol. 74(8), 1029–1036 (2018).
  Medline CASGoogle Scholar
• 25. Smith RL, Haslemo T, Refsum H et al. Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid-a large-scale study based on naturalistic therapeutic drug monitoring data. Eur. J. Clin. Pharmacol. 72(9), 1099–1104 (2016).
  Medline CASGoogle Scholar
• 26. Song C, Li X, Mao P et al. Impact of CYP2C19 and CYP2C9 gene polymorphisms on sodium valproate plasma concentration in patients with epilepsy. Eur. J. Hosp. Pharm. 29(4), 198–201 (2022).
  MedlineGoogle Scholar
• 27. Jiang D, Bai X, Zhang Q et al. Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling. Eur. J. Clin. Pharmacol. 65(12), 1187–1193 (2009).
  Medline CASGoogle Scholar
• 28. Du Z, Xu H, Zhao P et al. Influence of UGT2B7 and UGT1A6 polymorphisms on plasma concentration to dose ratio of valproic acid in Chinese epileptic children. Xenobiotica 51(7), 859–864 (2021).
  Medline CASGoogle Scholar
• 29. Inoue K, Suzuki E, Yazawa R et al. Influence of uridine diphosphate glucuronosyltransferase 2B7-161C>T polymorphism on the concentration of valproic acid in pediatric epilepsy patients. Ther. Drug Monit. 36(3), 406–409 (2014).
  Medline CASGoogle Scholar
• 30. Li X, Zhang J, Wu X et al. Polymorphisms of ABAT , SCN2A and ALDH5A1 may affect valproic acid responses in the treatment of epilepsy in Chinese. Pharmacogenomics 17(18), 2007–2014 (2016).
  CASGoogle Scholar
• 31. Rogawski MA, Loscher W. The neurobiology of antiepileptic drugs. Nat. Rev. Neurosci. 5(7), 553–564 (2004).
  Medline CASGoogle Scholar
• 32. Feng W, Mei S, Zhu L et al. Effects of UGT2B7 , SCN1A and CYP3A4 on the therapeutic response of sodium valproate treatment in children with generalized seizures. Seizure 58, 96–100 (2018).
  MedlineGoogle Scholar
• 33. Liu M, Mao J, Xu H et al. Effects of SCN1A and SCN2A polymorphisms on responsiveness to valproic acid monotherapy in epileptic children. Epilepsy Res. 168, 106485 (2020).
  Medline CASGoogle Scholar
• 34. Shi L, Zhu M, Li H et al. SCN1A and SCN2A polymorphisms are associated with response to valproic acid in Chinese epilepsy patients. Eur. J. Clin. Pharmacol. 75(5), 655–663 (2019).
  Medline CASGoogle Scholar
• 35. Haerian BS, Baum L, Tan HJ et al. SCN1A IVS5N+5 polymorphism and response to sodium valproate: a multicenter study. Pharmacogenomics 13(13), 1477–1485 (2012).
  CASGoogle Scholar
• 36. Lin CH, Ho CJ, Lu YT et al. Response to sodium channel blocking antiseizure medications and coding polymorphisms of sodium channel genes in Taiwanese epilepsy patients. BMC Neurol. 21(1), 367 (2021).
  MedlineGoogle Scholar
• 37. Ghazala E, Shahin DA, Wahba Y. Polymorphisms of the sodium voltage-gated channel, alpha subunit 1 ( SCN1A-A3184G ) gene among children with non-lesional epilepsy: a case-control study. Ital. J. Pediatr. 48(1), 157 (2022).
  Medline CASGoogle Scholar
• 38. Zhang H, Zhang W, Li Y et al. Correlations between UGT2B7*2 gene polymorphisms and plasma concentrations of carbamazepine and valproic acid in epilepsy patients. Brain Dev. 40(2), 100–106 (2018).
  MedlineGoogle Scholar
• 39. Oscarson M, McLellan RA, Gullstén H et al. Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population. FEBS Lett. 448(1), 105–110 (1999).
  Medline CASGoogle Scholar
• 40. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol. Bull. 37(Suppl. 2), 25–42 (2003).
  MedlineGoogle Scholar
• 41. Hung CC, Ho JL, Chang WL et al. Association of genetic variants in six candidate genes with valproic acid therapy optimization. Pharmacogenomics 12(8), 1107–1117 (2011).
  CASGoogle Scholar
• 42. Guo Y, Hu C, He X et al. Effects of UGT1A6 , UGT2B7 , and CYP2C9 genotypes on plasma concentrations of valproic acid in Chinese children with epilepsy. Drug Metab. Pharmacokinet. 27(5), 536–542 (2012).
  Medline CASGoogle Scholar
• 43. Munisamy M, Tripathi M, Behari M et al. The effect of uridine diphosphate glucuronosyltransferase (UGT)1A6 genetic polymorphism on valproic acid pharmacokinetics in Indian patients with epilepsy: a pharmacogenetic approach. Mol. Diagn. Ther. 17(5), 319–326 (2013).
  Medline CASGoogle Scholar
• 44. Wang Q, Zhao L, Liang M et al. Effects of UGT2B7 genetic polymorphisms on serum concentrations of valproic acid in Chinese children with epilepsy comedicated with lamotrigine. Ther. Drug Monit. 38(3), 343–349 (2016).
  Medline CASGoogle Scholar
• 45. Mei S, Feng W, Zhu L et al. Genetic polymorphisms and valproic acid plasma concentration in children with epilepsy on valproic acid monotherapy. Seizure 51, 22–26 (2017).
  MedlineGoogle Scholar
• 46. Chung JY, Cho JY, Yu KS et al. Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin. Pharmacol. Ther. 83(4), 595–600 (2008).
  Medline CASGoogle Scholar
• 47. Jain P, Shastri S, Gulati S et al. Prevalence of UGT1A6 polymorphisms in children with epilepsy on valproate monotherapy. Neurol. India 63(1), 35–39 (2015).
  MedlineGoogle Scholar
• 48. Wang Y, Li Z. Association of UGT2B7 and CaMK4 with response of valproic acid in Chinese children with epilepsy. Therapie 75(3), 261–270 (2020).
  MedlineGoogle Scholar
• 49. Du Z, Jiao Y, Shi L. Association of UGT2B7 and UGT1A4 polymorphisms with serum concentration of antiepileptic drugs in children. Med. Sci. Monit. 22, 4107–4113 (2016).
  Medline CASGoogle Scholar
• 50. Bűdi T, Tóth K, Nagy A et al. Clinical significance of CYP2C9 -status guided valproic acid therapy in children. Epilepsia 56(6), 849–855 (2015).
  Medline CASGoogle Scholar
• 51. Meisler MH, O'Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. J. Physiol. 588(Pt 11), 1841–1848 (2010).
  Medline CASGoogle Scholar