Effect of ABCB1 3435C>T transporter gene polymorphism on plasma efavirenz concentration in HIV-1 infected Thai adults

Sahapat Barusrux; Veeranoot Nissapatorn; Napatrupron Koomdee; Rattanaporn Sukprasong; Monpat Chamnanphon; Apichaya Puangpetch; Chonlaphat Sukasem; Napatrupron Koomdee; Rattanaporn Sukprasong; Monpat Chamnanphon; Apichaya Puangpetch; Chonlaphat Sukasem; Weerawat Manosuthi; Monpat Chamnanphon; Maria Pereira

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Effect of ABCB1 3435C>T transporter gene polymorphism on plasma efavirenz concentration in HIV-1 infected Thai adults

Author: Sahapat BARUSRUX ¹ ; Veeranoot NISSAPATORN ¹ ; Napatrupron KOOMDEE ² ; Rattanaporn SUKPRASONG ² ; Monpat CHAMNANPHON ² ; Apichaya PUANGPETCH ² ; Chonlaphat SUKASEM ² ; Napatrupron KOOMDEE ³ ; Rattanaporn SUKPRASONG ³ ; Monpat CHAMNANPHON ³ ; Apichaya PUANGPETCH ³ ; Chonlaphat SUKASEM ³ ; Weerawat MANOSUTHI ⁴ ; Monpat CHAMNANPHON ⁵ ; Maria PEREIRA ⁶
Author Information

1. School of Allied Health Sciences and Research Excellence Center for Innovation and Health Products, Walailak University
2. Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University
3. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital
4. Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health
5. Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University
6. CICECO-Aveiro Institute of Materials and Department of Medical Sciences, University of Aveiro
Publication Type:Journal Article
Keywords: ABCB1 3435C>T; Efavirenz; HIV-1; Thai; Transporter gene
From: Asian Pacific Journal of Tropical Medicine 2020;13(6):266-271
CountryChina
Language:Chinese
Abstract: Objective: To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1. Methods: A single nucleotide polymorphism of ABCB1 3435C>T (rs1045642) in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment. Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration. The relationship between plasma efavirenz concentrations and ABCB1 3435C>T polymorphisms was analyzed. Results: Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age, gender, body weight, CD4 count and plasma HIV-1 RNA, blood biochemical parameters, antiretroviral duration or ABCB1 3435C>T polymorphisms, except for height (OR=0.902, 95% CI: 0.835-0.973) (P<0.05). The minor allele frequency of ABCB1 3435C>T was 0.446. The frequency of the heterozygous mutant ABCB1 3435C/ T was 53.02% (n=79), ABCB1 3435T/T homozygous mutant was 18.12% (n=27) and the wild type ABCB1 3435C/C genotype was 28.86% (n=43). The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L [IQR: (1.46-4.12) mg/L]. The plasma concentration of efavirenz was higher in cases with ABCB1 3435T/T homozygous mutant [2.73 mg/L, IQR: (2.02-4.19) mg/L] and ABCB1 3435C/T heterozygous mutant [2.29 mg/L, IQR: (1.41-4.28) mg/L] genotypes compared to the wild type ABCB1 3435C/C homozygous [2.1 mg/L, IQR: (1.37-3.53) mg/L]. However, there was no statistically significant difference in the efavirenz concentration between the different genotypes (P>0.05). Conclusions: There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB1 3435T/T and ABCB1 3435C/T genotypes. No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.