Association of ABCB1 polymorphism with lamotrigine-resistant epilepsy in Thais

Abstract

Along with clinical and environmental factors, genetic variability in P-glycoprotein (P-gp) encoded by the ATP-binding cassette (ABC)B1 gene may influence inter-individual variability in antiepileptic drug response by limiting drug absorption and brain availability. Lamotrigine (LTG) is a new generation antiepileptic drug (AED) which has been reported to be transported through biological membranes by P-gp. Therefore, the aim of this study was to investigate the association of ABCB1 polymorphism along with clinical factors with LTG responsiveness. We recruited 104 Thai patients with epilepsy who were prescribed for LTG (68 LTG-resistant patients and 36 LTG-responders). The ABCB1 c.3435C>T (rs1045642) was genotyped. The association between the polymorphism and response to LTG was determined by multiple logistic regression. Multivariate logistic regression analyses showed that LTG resistance was associated with ABCB1 c.3435 CT and CC genotypes (OR 11.15, 95%CI 2.74-45.44, P = 0.001; OR 4.38, 95%CI 1.10-17.45, P = 0.036, respectively). Analysis of LTG monotherapy subgroup confirmed the association of ABCB1 c.3435 CT and CC genotypes with LTG-resistant patients (OR 23.36, 95%CI 2.09-260.93, P = 0.010; OR 15.14, 95%CI 1.27-180.46, P = 0.032, respectively). This study suggests that the ABCB1 c.3435C>T polymorphism influence the response of LTG in Thai patients with epilepsy.