Genotype and allele frequencies of ABCB1 and SLCO1B1 polymorphisms in THAI HIV-infected patients

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Noppaket Singkham
Anchalee Avihingsanon
Torsak Bunupuradah
Baralee Punyawudho

Abstract

Background : Genetic polymorphisms of protein transporters can alter the pharmacokinetics and pharmacodynamics of several substrate drugs including antiretrovirals (ARVs). The polymorphisms of ABCB1 and SLCO1B1 have been investigated in Caucasian and some of Asian populations. However, the information of
these single nucleotide polymorphisms (SNPs) in Thai population are limited.


Objective : The aim of this study was to determine the frequencies of the variant genotype and allele of ABCB1 and SLCO1B1 in Thai HIV-infected patients and to compare with the frequencies obtained from other populations.


Methods : Three SNPs: ABCB1 3435C>T, ABCB1 2677G>T and SLCO1B1 521T>C were identified by Taqman allelic discrimination assays using real time polymerase chain reaction system. Chi-square test was performed to
compare the distributions of observed genotypes with expected genotypes according to Hardy-Weinberg equilibrium and to compare the proportions of allele frequencies between our population and other ethnic populations.


Results : A total of 521 patients were included in this study. The homozygous variant genotypes were 22.50%, 29.75%, and 3.84% for ABCB1 3435TT, ABCB1 2677TT and SLCO1B1 521CC, respectively. The allele frequencies
of ABCB1 3435C>T, ABCB1 2677G>T and SLCO1B1 521T>C were 47.70%, 51.06%, and 11.90%, respectively. The prevalence of ABCB1 2677G>T was similar to other Asian populations, but the prevalence of ABCB1 3435C>T was different from the Chinese and the Korean populations. In addition, higher variant allele frequencies of ABCB1 3435T, ABCB1 2677T and SLCO1B1 521C were observed in Thais compared to African Americans.


Conclusion : We found that gene polymorphisms of ABCB1 and SLCO1B1 were frequent in Thai HIV-infected patients. These results could provide an evidence for future clinical studies regarding the variability in treatment responses and a risk of adverse effects of ARVs which are substrate of these transporters in Thai population.

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