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Relationship between CYP2C19 polymorphisms and weight gain in epilepsy patients treated with divalproex sodium: does gender matter?

  • Wardah Rahmatul Islamiyah ,
  • Nasronudin ,
  • Abdulloh Machin ,
  • Iin Ernawati ,
  • Paulus Sugianto ,

Abstract

Introduction: Epilepsy is an unprovoked seizure caused by an abnormal paroxysmal neuronal release in the brain. One of epilepsy treatments is anti-epileptic drug divalproex sodium. It is often prescribed to control seizures but it increases body weight. Weight gain may decrease the effectiveness of epilepsy treatment and cause endocrine disorders. CYP2C19 polymorphism may help physicians map patients vulnerable to weight gain due to divalproex sodium. This study aimed to determine the relationship between CYP2C19 polymorphisms and the incidence of weight gain based on gender in epilepsy patients treated with divalproex sodium.  

Methods: This cross-sectional study consisted of 17 male and 23 female patients. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify CYP2C19 polymorphism which was grouped into: extensive metabolizer, intermediate metabolizer and poor metabolizer. The results were analyzed using Chi-squared test to determine the relationship between CYP2C19 and each variable (gender, age, epilepsy types, valproic acid types, family history of obesity and presence of weight gain) based on of gender.

Results: The results showed that there was no statistically significant association between CYP2C19 polymorphisms and gender-based epilepsy patients groups (p>0.05). We found that most of the subjects in this study were women with an increase in body weight by 57.5%. There was no association of CYP2C19 polymorphism with type of divalproex sodium, dose of divalproex sodium, length of treatment, type of epilepsy and family history of obesity.

Conclusion: There is no significant association between CYP2C19 polymorphism and weight gain between genders in epilepsy patients.  

References

  1. Moshé SL, Perucca E, Ryvlin P, Tomson T. Epilepsy: new advances. Lancet [Internet]. 2015;385(9971):884–98. Available from: http://dx.doi.org/10.1016/s0140-6736(14)60456-6
  2. Banerjee PN, Filippi D, Allen Hauser W. The descriptive epidemiology of epilepsy-a review. Epilepsy Res [Internet]. 2009/04/15. 2009 Jul;85(1):31–45. Available from: https://pubmed.ncbi.nlm.nih.gov/19369037
  3. Sekarsari D, Kalanjati VP, Machin A, Gunawan PI. Profile Of Epilepsy Patients In Pediatric Ward At Dr. Soetomo General Academic Hospital, Surabaya, Indonesia In The Period Of January-December 2017. Maj Biomorfologi [Internet]. 2020;30(2):34. Available from: http://dx.doi.org/10.20473/mbiom.v30i2.2020.34-38
  4. Kurniawaty Y, Kalanjati VP. Mechanism of neurological disorders in epilepsy. Biomorfology Magazine. 2013;26(1):16-21.
  5. Ardianto C, Wardani HA, Nurrahmi N, Rahmadi M, Khotib J. Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice. Vet world [Internet]. 2020/05/22. 2020 May;13(5):963–6. Available from: https://pubmed.ncbi.nlm.nih.gov/32636594
  6. Ratri DMN, Rahmadi M, Islamiyah WR, Harum NF. Overview of therapeutic changes in antiepileptic drugs in adult patients. J Basic Clin Physiol Pharmacol [Internet]. 2020;30(6). Available from: http://dx.doi.org/10.1515/jbcpp-2019-0346
  7. Schwartz TL, Massa JL, Gupta S, Al-Samarrai S, Devitt P, Masand PS. Divalproex Sodium Versus Valproic Acid in Hospital Treatment of Psychotic Disorders. Prim Care Companion J Clin Psychiatry [Internet]. 2000 Apr;2(2):45–8. Available from: https://pubmed.ncbi.nlm.nih.gov/15014582
  8. Li H, Wang X, Zhou Y, Ni G, Su Q, Chen Z, et al. Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid. Int J Neuropsychopharmacol [Internet]. 2015 Mar 3;18(7):pyv021–pyv021. Available from: https://pubmed.ncbi.nlm.nih.gov/25740917
  9. Noai M, Soraoka H, Kajiwara A, Tanamachi Y, Oniki K, Nakagawa K, et al. Cytochrome P450 2C19polymorphisms and valproic acid-induced weight gain. Acta Neurol Scand [Internet]. 2015;133(3):216–23. Available from: http://dx.doi.org/10.1111/ane.12473
  10. Martin CK, Han H, Anton SD, Greenway FL, Smith SR. Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. J Psychopharmacol [Internet]. 2008/06/26. 2009 Sep;23(7):814–25. Available from: https://pubmed.ncbi.nlm.nih.gov/18583434
  11. Mahmud AA, Anu UH, Foysal KA, Hasan M, Sazib SM, Ragib AA, et al. Elevated serum malondialdehyde (MDA), insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH), and reduced antioxidant vitamins in polycystic ovarian syndrome patients. Narra J [Internet]. 2022;2(1). Available from: http://dx.doi.org/10.52225/narra.v2i1.56
  12. Verrotti A, Manco R, Agostinelli S, Coppola G, Chiarelli F. The metabolic syndrome in overweight epileptic patients treated with valproic acid. Epilepsia [Internet]. 2010;51(2):268–73. Available from: http://dx.doi.org/10.1111/j.1528-1167.2009.02206.x
  13. El-Khatib F, Rauchenzauner M, Lechleitner M, Hoppichler F, Naser A, Waldmann M, et al. Valproate, weight gain and carbohydrate craving: A gender study. Seizure [Internet]. 2007;16(3):226–32. Available from: http://dx.doi.org/10.1016/j.seizure.2006.12.009
  14. Luef G, Abraham I, Trinka E, Unterberger I, Hoppichler F, Bauer G, et al. Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology [Internet]. 2001;57(3):565.2-566. Available from: http://dx.doi.org/10.1212/wnl.57.3.565-a
  15. Grosso S, Mostardini R, Piccini B, Balestri P. Body Mass Index and Serum Lipid Changes During Treatment with Valproic Acid in Children with Epilepsy. Ann Pharmacother [Internet]. 2009;43(1):45–50. Available from: http://dx.doi.org/10.1345/aph.1l414
  16. Carlson JA, Dabiri G, Cribier B, Sell S. The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. Am J Dermatopathol [Internet]. 2011 Jul;33(5):433–60. Available from: https://pubmed.ncbi.nlm.nih.gov/21694502
  17. Borgquist A, Meza C, Wagner EJ. The role of AMP-activated protein kinase in the androgenic potentiation of cannabinoid-induced changes in energy homeostasis. Am J Physiol Endocrinol Metab [Internet]. 2014/12/30. 2015 Mar 15;308(6):E482–95. Available from: https://pubmed.ncbi.nlm.nih.gov/25550281
  18. Patterson M, Bloom SR, Gardiner J V. Ghrelin and appetite control in humans—Potential application in the treatment of obesity. Peptides [Internet]. 2011;32(11):2290–4. Available from: http://dx.doi.org/10.1016/j.peptides.2011.07.021
  19. Mani B, Nair PP, Sekhar A, Kamalanathan S, Narayan SK, Kesavan R. CYP2C19 & UGT1A6 genetic polymorphisms and the impact on Valproic acid-induced weight gain in people with epilepsy: Prospective genetic association study. Epilepsy Res [Internet]. 2021;177:106786. Available from: http://dx.doi.org/10.1016/j.eplepsyres.2021.106786
  20. Aruwatari J, Ishitsu T, Nakagawa K. Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy. Pharmaceuticals (Basel) [Internet]. 2010 Aug 20;3(8):2709–32. Available from: https://pubmed.ncbi.nlm.nih.gov/27713373
  21. Morrell MJ, Giudice L, Flynn KL, Seale CG, Paulson AJ, Doñe S, et al. Predictors of ovulatory failure in women with epilepsy. Ann Neurol [Internet]. 2002;52(6):704–11. Available from: http://dx.doi.org/10.1002/ana.10391
  22. Isojärvi JIT, Laatikainen TJ, Knip M, Pakarinen AJ, Juntunen KTS, Myllyla V V. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol [Internet]. 1996;39(5):579–84. Available from: http://dx.doi.org/10.1002/ana.410390506
  23. van der Sande MA. A template for improved prevention and control of cardiovascular disease in sub-Saharan Africa. Health Policy Plan [Internet]. 2001;16(4):345–50. Available from: http://dx.doi.org/10.1093/heapol/16.4.345
  24. McIntyre RS, Konarski JZ, Keck PE. Psychotropic-Induced Weight Gain: Liability, Mechanisms and Treatment Approaches [Internet]. Obesity and Mental Disorders. Informa Healthcare; 2006. p. 307–54. Available from: http://dx.doi.org/10.3109/9780849374517.014
  25. Hirschberg AL. Sex hormones, appetite and eating behaviour in women. Maturitas [Internet]. 2012;71(3):248–56. Available from: http://dx.doi.org/10.1016/j.maturitas.2011.12.016
  26. Choi MH, Skipper PL, Wishnok JS, Tannenbaum SR. Characterization of testosterone 11β-hydroxylation catalyzed by human liver microsomal cytochromes P450. Drug metab dispos [Internet]. 2005;33(6):714–8. Available from: http://dx.doi.org/10.1124/dmd.104.003327
  27. Muftuoglu Y, Mustata G. Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis. Reprod Biol Endocrinol [Internet]. 2011 Jun 21;9:92. Available from: https://pubmed.ncbi.nlm.nih.gov/21693043
  28. Usmani KA, Rose RL, Hodgson E. Inhibition and Activation of the Human Liver Microsomal and Human Cytochrome P450 3A4 Metabolism of Testosterone by Deployment-Related Chemicals. Drug Metab Dispos [Internet]. 2003;31(4):384–91. Available from: http://dx.doi.org/10.1124/dmd.31.4.384

How to Cite

Islamiyah, W. R., Nasronudin, Machin, A. ., Ernawati, I., & Sugianto, P. . (2022). Relationship between CYP2C19 polymorphisms and weight gain in epilepsy patients treated with divalproex sodium: does gender matter?. Bali Medical Journal, 11(3), 1800–1804. https://doi.org/10.15562/bmj.v11i3.3748

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