Prevalence of UGT1A4 and UGT2B7 polymorphisms in Thai patients

Abstract

Background : UGT1A4 and UGT2B7 play an important role in the metabolism of several endogenous substrates and xenobiotics including clozapine, morphine and lamotrigine. The polymorphisms of UGT1A4 and UGT2B7 may be associated with the variability of glucuronidation activity which leads to the interindividual variability of lamotrigine concentrations among patients. Even though, there is an evidence of the variation of UGT polymorphisms between races, the information of UGT polymorphisms in Thai population is limited.

Objective : To investigate the frequencies of UGT1A4 and UGT2B7 polymorphisms 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, UGT1A4 70C>T, UGT2B7 372A>G, and UGT2B7 -161C>T were identified. Genotyping was carried out by Taqman allelic discrimination assays using Taqman probes. Chi-square tests were used to assess the distribution of the observed genotypes according to Hardy- Weinberg equilibrium and to compare the allele frequencies between the Thais and other populations.

Results : There were 81 patients included in this study. The allele frequencies of UGT1A4 142T>G, UGT2B7 372A>G and UGT2B7 -161C>T were 27%, 20%, and 25%, respectively. The polymorphism of UGT1A4 70C>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 of UGT1A4 70C>T, UGT2B7 372A>G, and UGT2B7 -161C>T are similar to the values previously reported in other Asian populations, but the frequency of UGT1A4 142T>G in this Thai population is higher than those of other Asian populations. Our findings provide initial information for designing studies for investigating the association between genetic factors and pharmacokinetics of these UGTs substrates.