The effect of patient’s characteristics on CYP2C19 polymorphisms based on weight and gender groups of epileptic seizure patients taking divalproex sodium
Keywords:
CYP2C19 polymorphism, epilepsy, body weight, gender, valproic acidAbstract
Valproic acid (VPA) is one of the most commonly used antiepileptic drugs and has broad indications for various types of epilepsy. Despite its broad spectrum, one of the most widely reported side effects of VPA is weight gain. The aim of this study was to determine the effect of demographic characteristics on genetic factors of CYP2C19 polymorphism in gender and weight changes. The research method used is analytic observational with a cross sectional study design involving two different groups and compared at the same time. Statistical analysis in this study using multiple linear regression. In observational results, it was known that the type of valproic acid (regular valproic acid and extended release) and free testosterone levels had a statistically significant effect on CYP2C19 polymorphisms (p < 0.05) in the body group. Meanwhile, in the gender group, it was found that female gender with a family history of obesity had a significant influence on the incidence of CYP2C19 polymorphisms, while characteristics such as age, dose, duration of therapy, type of epilepsy, free-testosterone levels, and total estradiol levels did not have a significant effect on CYP2C19 polymorphisms. Cytochrome (CYP) P450 enzymes play an important role in VPA metabolism).
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Bialer, M. (2007). Extended-release formulations for the treatment of epilepsy. CNS drugs, 21(9), 765-774.https://doi.org/10.2165/00023210-200721090-00005
Borgquist, A., Meza, C., & Wagner, E. J. (2015). The role of AMP-activated protein kinase in the androgenic potentiation of cannabinoid-induced changes in energy homeostasis. American Journal of Physiology-Endocrinology and Metabolism, 308(6), E482-E495.https://doi.org/10.1152/ajpendo.00421.2014
Bowden, C. L., Swann, A. C., Calabrese, J. R., Rubenfaer, L. M., Wozniak, P. J., Collins, M. A., ... & Saltarelli, M. (2006). A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. Journal of Clinical Psychiatry, 67(10), 1501-1510.
El-Khatib, F., Rauchenzauner, M., Lechleitner, M., Hoppichler, F., Naser, A., Waldmann, M., ... & Luef, G. J. (2007). Valproate, weight gain and carbohydrate craving: a gender study. Seizure, 16(3), 226-232.https://doi.org/10.1016/j.seizure.2006.12.009
Fui, M. N. T., Dupuis, P., & Grossmann, M. (2014). Lowered testosterone in male obesity: mechanisms, morbidity and management. Asian journal of andrology, 16(2), 223.https://doi.org/10.4103%2F1008-682X.122365
Jaeri, S., & Islamiyah, W. R. (2018). The potential mechanisms of effect of valproic acid on lipid profiles: An updated review. Journal of Epileptology, 26(1-2), 49-55.
Li, H., Wang, X., Zhou, Y., Ni, G., Su, Q., Chen, Z., ... & Huang, M. (2015). Association of LEPR and ANKK1 gene polymorphisms with weight gain in epilepsy patients receiving valproic acid. International Journal of Neuropsychopharmacology, 18(7), pyv021. https://doi.org/10.1093/ijnp/pyv021
Leppik, I. E., & Hovinga, C. A. (2013). Extended‐release antiepileptic drugs: a comparison of pharmacokinetic parameters relative to original immediate‐release formulations. Epilepsia, 54(1), 28-35.https://doi.org/10.1111/epi.12043
Mangla, A. G., Dhamija, N., Gupta, U., & Dhall, M. (2019). Familial Background as a Hidden Cause for Obesity among College Going Girls. Journal of Biosciences and Medicines, 7(04), 1. Doi:10.4236/jbm.2019.74001
Mani, B., Nair, P. P., Sekhar, A., Kamalanathan, S., Narayan, S. K., & Kesavan, R. (2021). CYP2C19 & UGT1A6 genetic polymorphisms and the impact on Valproic acid-induced weight gain in people with epilepsy: Prospective genetic association study. Epilepsy Research, 177, 106786.https://doi.org/10.1016/j.eplepsyres.2021.106786
Martin, C. K., Han, H., Anton, S. D., Greenway, F. L., & Smith, S. R. (2009). Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. Journal of psychopharmacology, 23(7), 814-825.https://doi.org/10.1177%2F0269881108091595
Miftahussurur, M., Doohan, D., Syam, A. F., Nusi, I. A., Subsomwong, P., Waskito, L. A., ... & Yamaoka, Y. (2021). CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes. Biology, 10(4), 300. MDPI AG. https://doi.org/10.3390/biology10040300
Noai, M., Soraoka, H., Kajiwara, A., Tanamachi, Y., Oniki, K., Nakagawa, K., ... & Saruwatari, J. (2016). Cytochrome P450 2C19 polymorphisms and valproic acid‐induced weight gain. Acta Neurologica Scandinavica, 133(3), 216-223.https://doi.org/10.1111/ane.12473
Saruwatari, J., Ishitsu, T., Seo, T., Shimomasuda, M., Okada, Y., Goto, S., ... & Nakagawa, K. (2010). The clinical impact of cytochrome P450 polymorphisms on anti-epileptic drug therapy. Epilepsy & Seizure, 3(1), 34-50.https://doi.org/10.3805/eands.3.34
Smith, M. L. (2010). Neuropsychology in epilepsy: children are not small adults. Epilepsia, 51, 68-69. https://doi.org/10.1111/j.1528-1167.2009.02451.x
Stingl, J. C., Scholl, C., Bosch, J. E., & Viviani, R. (2021). Genetic polymorphism of CYP2C19 and subcortical variability in the human adult brain. Translational Psychiatry, 11(1), 1-5.https://doi.org/10.1038/s41398-021-01591-5
Tan, L., Yu, J. T., Sun, Y. P., Ou, J. R., Song, J. H., & Yu, Y. (2010). The influence of cytochrome oxidase CYP2A6, CYP2B6, and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients. Clinical neurology and neurosurgery, 112(4), 320-323.https://doi.org/10.1016/j.clineuro.2010.01.002
Verrotti A, Manco R, Agostinelli S, Coppola G, Chiarelli F. The metabolic syndrome in overweight epileptic patients treated with valproic acid. Epilepsia. 2010 Feb;51(2):268-73.https://doi.org/10.1111/j.1528-1167.2009.02206.x
Zhu, M. M., Li, H. L., Shi, L. H., Chen, X. P., Luo, J., & Zhang, Z. L. (2017). The pharmacogenomics of valproic acid. Journal of human genetics, 62(12), 1009-1014.https://doi.org/10.1038/jhg.2017.91
Zhang, L., & Wang, Y. (2021). Gene therapy in epilepsy. Biomedicine & Pharmacotherapy, 143, 112075. https://doi.org/10.1016/j.biopha.2021.112075
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