ࡱ> 8:7q` bjbjqPqP7::( @@@@,l 7 7 7 $h59_  "7 _ _ 5n6_ _ x r]Xt@M.<{D7 h J <% :7 7 7 55 7 7 7 _ _ _ _ DD  SNP analysis in a drug-transporter gene (ATP-binding cassette family ABCC2) suggest pharmacoresistence association in mesial temporal lobe epilepsy patients Mariana S. Silva1, Kellen M. Siqueira1, Elisabeth Bilevicius2, Rodrigo Secolin1, Marilza S. Santos1, Fernando Cendes2, Iscia Lopes-Cendes1 1. Department of Medical Genetics; 2. Department of Neurology; Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. Introduction: Mesial temporal lobe epilepsy (MTLE), the most common form of partial epilepsies, is associated with a high proportion of drug-resistant patients. One hypothesis to explain differences in response to antiepileptic drugs (AEDs) is pharmacogenetic differences in genes related to drug-metabolism. Therefore, allelic variations in these genes could be responsible for decreased efficacy of AEDs and failure to control seizures. The purpose of this study was to investigate whether single nucleotide polymorphisms (SNPs) in a drug-transporter gene (ATP-binding cassette family, ABCC2) could be associated with pharmacoresistance to AEDs in a large group of patients with MTLE. Methods: Consecutive patients with clinical-EEG diagnosis of MTLE were ascertained at the epilepsy clinic of our University Hospital. We included a total of 101 drug-resistant MTLE patients and compared with 64 drug-responsive MTLE patients who were seizure free on AEDs. We genotyped 6 SNPs from the dbSNPs database within the ABCC2 gene: rs3740065(T/C), rs3740066(C/T), rs3740067(C/G), rs2273697(A/G), rs2756104 (C/T), rs2756109 (G/T). Genotyping was carried out using the TaqMan system"! (Applied Biosystems). We assessed the significance of genotypic and allelic association using logistic regression. Results: Genotypic frequencies were in Hard-Weinberg equilibrium for both groups. Logistic regression showed a significant association between an intronic SNP (rs3740067) at the ABCC2 gene and pharmacoresistance to AEDs (p=0.0015); OR = 4.90 (95% CI: 1.48 16.2). 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