Association of ABCB1 and NR1I2 polymorphisms with response to carbamazepine in Malaysian epilepsy patients

Abstract

The human nuclear pregnane X receptor (PXR;NR1I2) which regulates the expression of ABCB1 gene which encodes phosphoglycoprotein, an efflux pump for carbamazepine (CBZ). The aim of this study was to investigate whether ABCB1 C3435T and NR1I2 A7635G variants significantly impact the response of epilepsy patients to CBZ monotherapy. ABCB1 C3435T and NR1I2 A7635G genotyping were performed on 168 Malaysian epilepsy subjects (76 drug‐responsive and 92 drug‐resistant) receiving CBZ monotherapy by PCR‐RFLP. The results for C3435T revealed a genotype distribution of CC, CT, TT: 39.5%, 43.4%, 17.1% for drug‐resistant patients compared to CC, CT, TT: 29.3%, 58.7%, 12.0% for drug‐responsive patients. The genotypes distribution of A7635G in the drug‐resistant patients for AA, AG, and GG were 13.0%, 39.1%, 47.8% and in drug‐responsive patients 10.5%, 57.9%, 31.6%, respectively. Furthermore, among drug‐resistants and drug‐responsive patients, the frequency of carriers of T allele and was 41.3.1% and 38.8% and for G allele 67.4% and 60.5%, respectively. The association of genotype and allele frequencies in C3435T and A7635G with response to CBZ was nonsignificant. In conclusion, the allelic and genotype analysis in Malaysian epilepsy patients suggests that the NR1I2 A7635G and ABCB1 C3435T polymorphisms are not associated with resistance to CBZ.