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Chulalongkorn Medical Journal

Abstract

Background : UGT1A4 and UGT2B7 play an important role in the metabolism ofseveral endogenous substrates and xenobiotics including clozapine,morphine and lamotrigine. The polymorphisms of UGT1A4 andUGT2B7 may be associated with the variability of glucuronidationactivity which leads to the interindividual variability of lamotrigineconcentrations among patients. Even though, there is an evidenceof the variation of UGT polymorphisms between races, the informationof UGT polymorphisms in Thai population is limited.Objective : To investigate the frequencies of UGT1A4 and UGT2B7polymorphisms in Thai patients.Setting : Prasat Neurological Institute, Bangkok.Research design : Prospective descriptive study.Patients : Patients with epilepsy and psychiatric disorder were included.Methods : Four single nucleotide polymorphisms, UGT1A4 142T>G, UGT1A470C>T, UGT2B7 372A>G, and UGT2B7 -161C>T were identified.Genotyping was carried out by Taqman allelic discrimination assaysusing Taqman probes. Chi-square tests were used to assessthe distribution of the observed genotypes according to Hardy-Weinberg equilibrium and to compare the allele frequencies betweenthe Thais and other populations.Results : There were 81 patients included in this study. The allele frequenciesof UGT1A4 142T>G, UGT2B7 372A>G and UGT2B7 -161C>T were27%, 20%, and 25%, respectively. The polymorphism of UGT1A470C>T was not detected in this population.Conclusion : Nearly half of the patients are wild-type of UGT1A4 142T>G,UGT2B7 372A>G and UGT2B7 -161C>T. The allele frequencies ofUGT1A4 70C>T, UGT2B7 372A>G, and UGT2B7 -161C>T aresimilar to the values previously reported in other Asian populations,but the frequency of UGT1A4 142T>G in this Thai population ishigher than those of other Asian populations. Our findings provideinitial information for designing studies for investigating the associationbetween genetic factors and pharmacokinetics of these UGTssubstrates.

Publisher

Faculty of Medicine, Chulalongkorn University

First Page

49

Last Page

60

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