TY - JOUR

T1 - Influence Of The Polymorphism In CYP2C9, CYP2C19 And MDR1 On Risk Of Development Of Side Effects Due To Valproic Acide In Patients With Epilepsy

AU - Сергеева, Татьяна Васильевна

PY - 2019

Y1 - 2019

N2 - Purpose : Decrease of frequency and weight of the side effects at therapy by valproic acide in mono and polytherapies in patients with epilepsy. Method : We examined 113 patients aged from 4 up to 57 years with epilepsy accepting valproic acide in monotherapy of 35.8% or polytherapy — 64.2% (Carbamazepin or topiramate). Average age of patients was 27 years, 49 men (43.4%) and 64 women (56.6%). The genetic form of epilepsy was diagnosed for 55 patients (49%), at 55 patients (49%) structural epilepsy, is diagnosed for 3 patients (2%) - not specified. Using of the PCR- RFLP analysis polymorphisms in genes of valproic acid metabolism were studied in patients with epilepsy and in North- Western region population of Russian Federation: P- glycoprotein — MDR1 ( 3435C > T ), cytochromes P450 — CYP2C9 ( 430C > T 1075A > C ) and CYP2C19 (681G > A) . Assessment of dynamics of undesirable side effects was made objective and on the basis of complaints of patients in the course of the research at repeated visits to the attending physician, the reduced Naranzho′s scale was used (the question of placebo was excluded from poll). Results : As compared with unaffected patients, in people with chronic adverse events statistically significant increase of «mutant» allele in gene CYP2C9 (1075A > C) was identified (3.5% and 14.5%, respectively, F  <  0.03). The interrelation between a pharmakorezistent at treatment of patients with epilepsy and a polymorphism of genes of P- 450 cytochromes ( CYP2C9, CYP2C19 ) and MDR1 wasn′t revealed. Conclusion : The prospects of pharmacogenetic testing at epilepsy consist in creation of set of gaplotip for initial determination of risk of development of the undesirable phenomena against the background of therapy by various medicines that in the future will allow the personalized medicine to take the central place in clinical practice. Application of pharmacogenetic testing can raise a treatment compliance.

AB - Purpose : Decrease of frequency and weight of the side effects at therapy by valproic acide in mono and polytherapies in patients with epilepsy. Method : We examined 113 patients aged from 4 up to 57 years with epilepsy accepting valproic acide in monotherapy of 35.8% or polytherapy — 64.2% (Carbamazepin or topiramate). Average age of patients was 27 years, 49 men (43.4%) and 64 women (56.6%). The genetic form of epilepsy was diagnosed for 55 patients (49%), at 55 patients (49%) structural epilepsy, is diagnosed for 3 patients (2%) - not specified. Using of the PCR- RFLP analysis polymorphisms in genes of valproic acid metabolism were studied in patients with epilepsy and in North- Western region population of Russian Federation: P- glycoprotein — MDR1 ( 3435C > T ), cytochromes P450 — CYP2C9 ( 430C > T 1075A > C ) and CYP2C19 (681G > A) . Assessment of dynamics of undesirable side effects was made objective and on the basis of complaints of patients in the course of the research at repeated visits to the attending physician, the reduced Naranzho′s scale was used (the question of placebo was excluded from poll). Results : As compared with unaffected patients, in people with chronic adverse events statistically significant increase of «mutant» allele in gene CYP2C9 (1075A > C) was identified (3.5% and 14.5%, respectively, F  <  0.03). The interrelation between a pharmakorezistent at treatment of patients with epilepsy and a polymorphism of genes of P- 450 cytochromes ( CYP2C9, CYP2C19 ) and MDR1 wasn′t revealed. Conclusion : The prospects of pharmacogenetic testing at epilepsy consist in creation of set of gaplotip for initial determination of risk of development of the undesirable phenomena against the background of therapy by various medicines that in the future will allow the personalized medicine to take the central place in clinical practice. Application of pharmacogenetic testing can raise a treatment compliance.

M3 - Article

VL - 60

SP - 174

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 11

Y2 - 22 June 2019 through 24 June 2019

ER -