Abstracts

Role of MDR1 C3435T gene polymorphism in seizure occurrence and its effect on Anti-Epileptic Drug (PHT) absorption

Abstract number : 2.262
Submission category : 7. Antiepileptic Drugs
Year : 2011
Submission ID : 14995
Source : www.aesnet.org
Presentation date : 12/2/2011 12:00:00 AM
Published date : Oct 4, 2011, 07:57 AM

Authors :
S. Ponnala, J. Chaudhari, J. Ahmed, D. Biladvala, P. Kaipa, Q. Hasan

Rationale: To evaluate the MDR1 C3435T gene polymorphism in generalized seizure (GS) and febrile seizure (FS) patients to assess its role in seizure susceptibility and to evaluate its role in absorption of anti-epileptic drug, Phenytoin (PHT) in a cohort of patients. Methods: cases of seizure (86 GS and 41 FS) patients were analyzed for GABRG2 C588T gene polymorphism using RFLP-PCR. Serum PHT levels were analyzed.Results: MDR1 3435T allele was significantly associated with GS in Indian population (p<0.05) compared to FS and controls. From the data, CT and TT genotype carriers of GS had recurrent seizures compared to others. T allele carriers in seizure recurrent (SR) group of GS and FS were high compared to well control seizure group. TT genotype carriers in SR group were high in FS compared to well control seizure group. MDR1 C3435T gene polymorphism affects serum PHT levels (p<0.015). Association of dose PHT ratio and genotype groups of MDR1 C3435T gene polymorphism showed a significant association (p<0.05). MDR1*CC genotype was more common in cases with low serum PHT levels. Also it is evident that CT and TT genotype carriers have high percentage of SR with elevated serum PHT levels. Conclusions: Our results show that the MDR1 3435T allele s role in seizure occurrence and in PHT absorption. We suggest dose adjustment based on MDR1 C3435T genotyping, especially at the induction of therapy, would be of value in order to lower the risk of concentration dependent drug toxicity in patients.
Antiepileptic Drugs