title: Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis.
abstract: The human major vault protein (MVP) has been implicated in the development of drug resistance in cancer cells. Over expression of MVP has also been reported in brain tissue samples from antiepileptic drug (AED)-resistant human focal epilepsies. To investigate the relationship between single nucleotide polymorphisms (SNPs) involving the MVP gene and AED-resistance, we compared the distribution of three SNPs in the MVP gene, rs4788187, rs3815824 and rs3815823, among 220 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype of AED-resistant epilepsy syndrome), 201 patients with juvenile myoclonic epilepsy (JME) (prototype of AED-responsive epilepsy syndrome) and 213 ethnically matched non-epilepsy controls. All the patients and controls were residents of the South Indian state of Kerala for more than three generations. We did not find any significant difference in allele and genotypic frequencies of the studied SNPs between AED-resistant and AED-responsive cohorts, and between AED-resistant and AED-responsive cohorts independently and pooled together when compared with the controls. We conclude that rs4788187, rs3815824, rs3815823 variants of the MVP gene are associated neither with predisposition for epilepsy nor with AED-resistance in the population that we have studied. Our results suggest the need for further research into the link between MVP and AED-resistance.
authors.affiliation: R. Madhavan Nayar Center for Comprehensive Epilepsy Care, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Shabeesh
authors.initials: S
authors.lastname: Balan
authors.forename: Saradalekshmi Koramannil
authors.initials: SK
authors.lastname: Radhab
authors.forename: Koramannil
authors.initials: K
authors.lastname: Radha
authors.forename: Sanish
authors.initials: S
authors.lastname: Sathyan
authors.forename: Joseph
authors.initials: J
authors.lastname: Vijai
authors.forename: Moinak
authors.initials: M
authors.lastname: Banerjee
authors.forename: Kurupath
authors.initials: K
authors.lastname: Radhakrishnan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000927:Anticonvulsants / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012598:Sclerosis; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D055815:Young Adult; D000099187:Major Vault Protein
chemical_list: D000927:Anticonvulsants; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
keywords: ABC; AED; ATL; ATP-binding cassette; Anterior temporal lobectomy; Anti-epileptic drug; Drug resistance; EEG; Electroencephalogram; Genetic variants; JME; Juvenile myoclonic epilepsy; LD; Linkage disequilibrium; MTLE-HS; MVP; Major vault protein; Mesial temporal lobe epilepsy with hippocampal sclerosis; SNP; Single nucleotide polymorphism; Temporal lobe epilepsy