BIOMAT Database Logo BIOMAT Database Logo

Role of MDR1 C3435T and GABRG2 C588T gene polymorphisms in seizure occurrence and MDR1 effect on anti-epileptic drug (phenytoin) absorption. 2012

Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA. sponnala@uic.edu

OBJECTIVE To assess the role of MDR1 and gamma-aminobutyric acid receptor-gamma 2 sub unit (GABRG2) gene polymorphism in seizure susceptibility in generalized seizure (GS) and febrile seizure (FS) patients and to evaluate MDR1 C3435T gene polymorphism's role in absorption of the anti-epileptic drug, phenytoin (PHT) in a cohort of patients. METHODS One hundred twenty-seven cases of seizure (86 GS and 41 FS) patients were analyzed for MDR1 C3435T and GABRG2 C588T gene polymorphisms using restriction fragment length polymorphism-polymerase chain reaction. Serum PHT levels were analyzed. RESULTS The T allele of MDR1 C3435T and GABRG2 C588T gene polymorphism was higher in GS in the Indian population compared with controls. From the data in GS, CT and TT genotype carriers of the MDR1 gene and TT genotype carriers of the GABRG2 gene had more recurrent seizures compared with others. MDR1 T allele carriers in the seizure reoccurrence (SR) group of GS and FS were high compared with the well-controlled seizure group (with no seizures after treatment). TT genotype carriers in SR group were high in FS (with regard to MDR1 gene polymorphism) and GS (with regard to GABRG2 gene polymorphism) compared with a well-controlled 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.In addition, it is evident that CT and TT genotype carriers have a high percentage of SR with elevated serum PHT levels. CONCLUSIONS Our results show that the MDR1 3435T and GABRG2 588T alleles play a role in seizure occurrence. Moreover, the MDR1 3435T allele also affects PHT absorption. We suggest MDR1 C3435T and GABRG2 C588T genotyping would be of value in order to lower the risk of concentration-dependent drug toxicity and for better patient management.

UI MeSH Term Description Entries
D007194 India A country in southern Asia, bordering the Arabian Sea and the Bay of Bengal, between Burma and Pakistan. The capitol is New Delhi. Republic of India
D007223 Infant A child between 1 and 23 months of age. Infants
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children

Related Publications

Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
Analysis of GABRG2 C588T polymorphism in genetic epilepsy and evaluation of GABRG2 in drug treatment.
September 2021, Clinical and translational science,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
The likelihood approach for potential role of "GABRG2 (C588T, C315T) gene polymorphisms" on the poor response to carbamazepine therapy in Pakhtun population of Pakistan.
October 2022, Medicine,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
Frequency of G2677T/A and C3435T polymorphisms of MDR1 gene in preeclamptic women.
September 2013, Ginekologia polska,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
Significance of MDR1 gene polymorphism C3435T in predicting drug response in epilepsy.
February 2014, Epilepsy research,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
CYP3A5*3 and C3435T MDR1 polymorphisms in prognostication of drug-resistant epilepsy in children and adolescents.
January 2013, BioMed research international,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
Anti-Epileptic Drug Combination Efficacy in an In Vitro Seizure Model - Phenytoin and Valproate, Lamotrigine and Valproate.
January 2017, PloS one,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
Frequency of the C1236T, G2677T/A and C3435T MDR1 gene polymorphisms in the Serbian population.
January 2011, Pharmacological reports : PR,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
The drug-transporter gene MDR1 C3435T and G2677T/A polymorphisms and the risk of multidrug-resistant epilepsy in Turkish children.
January 2014, Molecular biology reports,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
Tacrolimus dosing in Chinese renal transplant patients is related to MDR1 gene C3435T polymorphisms.
November 2006, Transplantation proceedings,
Shivani Ponnala, and Jaydip Ray Chaudhari, and Momin Abdul Jaleel, and Dilnawaz Bhiladvala, and Prabhakar Rao Kaipa, and Undurti N Das, and Qurratulain Hasan
C3435T polymorphism of MDR1 gene with warfarin resistance.
October 2013, Clinica chimica acta; international journal of clinical chemistry,
Copied contents to your clipboard!