Polymorphisms of ABCC2, ABCC4, ABCC10 and SLC22A6 in Thai HIV - infected patients

Abstract

Background : Drug transporters including ABCC2, ABCC4, ABCC10 and SLC22A6 play important roles in regulating physiologic solute and fluid balance in the cell. They also involve in drug delivery into the organs. Therefore, genetic variations of these transporters may influence the pharmacokinetics of drugs and major pharmacological active metabolites. The information of transporter gene polymorphisms can be useful as guidance for the study of the association between genetic variations and pharmacokinetics of drugs.

Objective : To determine the allele frequency of ABCC2, ABCC4, ABCC10 and SLC22A6 in Thai HIV - infected patients.

Research design : Cross-sectional study.

Setting : The HIV Netherlands Australia Thailand Research Collaboration (HIVNAT), Bangkok, Thailand.

Patients : The study enrolled 400 Thai HIV - infected patients from the HIV - NAT from January 1st to September 1st, 2012.

Methods : Nine single nucleotide polymorphisms (SNPs) including ABCC2-24C>T; 1249G>A; 3563T>A; 3972C>T, ABCC4 3463A>G; 4131T>G, ABCC10 526G>A; 2759T>C and SLC22A6 728G>A were investigated. The genotyping was performed by Taqman allelic discrimination assays with fluorogenic probes. All reactions were analyzed by Applied Biosystems 7500 Real-Time PCR System. The deviation of polymorphisms according to Hardy-Weinberg equilibrium was tested using Chi-square test. The comparisons of the allele frequencies between Thai and other populations were performed using Chi-square tests.

Results : The allele frequencies of ABCC2 -24C>T; 1249G>A; 3563T>A; 3972C>T, ABCC4 3463A>G; 4131T>G, ABCC10 526G>A and 2759T>C in this population were 21.8%, 7.8%, 0.1%, 24.9%, 19.8%, 49.2%, 51% and 7.1%, respectively. The polymorphism of SLC22A6 728G>A was not found in this population.

Conclusion : The prevalence of the polymorphisms examined in this study was similar to those observed among Asian populations. However, they were different from the Caucasian and African populations. The influence of these polymorphisms on pharmacokinetics requires further investigation.