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Clinical treatment with antiepileptics exhibits large interpatient variability. The UDP-glucuronosyltransferase (UGT) 1A4 is an enzyme responsible for the conjugation of glucuronic acid in diverse functional groups included in various antiepileptic drugs, such as lamotrigine and phenytoin. Several genetic polymorphisms of UGT1A4 have been described in different populations; among them, two non-synonymous single nucleotide polymorphisms (SNPs) 70A>C (P24T; UGT1A4*2) and 142T>G (L48V; UGT1A4*3b), as well as a synonymous variant SNP 471T>C (C157C; UGT1A4*1b). P24T and L48V polymorphisms reduce the glucuronidation activity on various substrates. Recently, it has been shown that L48V polymorphism decreases the serum concentration of lamotrigine in patients on monotherapy or polytherapy, resulting in clinical outcome variability. The main goal of this study was to determine the allelic frequencies of UGT1A4*1b, UGT1A4*2 and UGT1A4*3b in a sample of Mexican Mestizo (MM) and Spaniard (SP) healthy volunteers. UGT1A4 genotyping is clinically important in order to identify patients who may be at an increased risk for failure of therapy and/or adverse effects to anticonvulsants such as phenytoin and lamotrigine. In this study, the allelic frequencies of these three UGT1A4 variants were determined by combined methodology of RFLPs and RT-PCR in MM and SP populations. The allelic frequencies of the three UGT1A4 polymorphisms analyzed showed interethnic differences between MM and SP, that was statistically significant for UGT1A4*1b (0.17 and 0.08, respectively; p=0.002). These data could help clinicians to improve clinical response during treatment with UGT1A4 antiepileptic drug substrates in these populations.