A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups
Date
2009
Authors
Parathyras J.
Gebhardt S.
Hillermann-Rebello R.
Grobbelaar N.
Venter M.
Warnich L.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
South Africa, like many other Southern African countries, has one of the highest HIV infection rates in the world and many individuals consequently receive antiretroviral therapy (ART). However, knowledge regarding (i) the prevalence of functional single nucleotide polymorphisms (SNPs) in pharmacologically relevant genes, and (ii) variance in pharmacotherapy both within and between different populations and ethnic groups is limited. The aim of this study was to determine whether selected polymorphisms in cytochrome P450 (CYP) genes (CYP2B6 and CYP3A4) and the multidrug-resistance 1 (ABCB1) gene underlie altered antiretroviral (ARV) drug response in two South African populations. DNA samples from 182 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity on ART were genotyped for the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in ABCB1. Univariate two-way analysis of variance (ANOVA) testing revealed no apparent effect of ethnicity on immune recovery (in terms of CD4-cell count) in response to ART. Univariate one-way ANOVA testing revealed a discernible effect of genotype on immune recovery in the cases of the T-129C (P0.03) and G2677A (P0.01) polymorphisms in the ABCB1 gene. This study serves as a basis for better understanding and possible prediction of pharmacogenetic risk profiles and drug response in individuals and ethnic groups in South Africa. © 2009 The Japan Society of Human Genetics. All rights reserved.
Description
Keywords
antiretrovirus agent, CD4 antigen, cytochrome P450, cytochrome P450 2B6, cytochrome P450 3A4, efavirenz, lamivudine, multidrug resistance protein 1, nevirapine, stavudine, zidovudine, analysis of variance, article, backache, CD4 lymphocyte count, cerebral blindness, controlled study, convulsion, diplopia, dizziness, drug response, drug withdrawal, ethnicity, fatigue, genetic polymorphism, genotype, hepatomegaly, highly active antiretroviral therapy, human, Human immunodeficiency virus infected patient, Human immunodeficiency virus infection, lactic acidosis, lipodystrophy, major clinical study, nausea, peripheral neuropathy, pharmacogenetics, pruritus, rash, single nucleotide polymorphism, South Africa, treatment response, univariate analysis, African Continental Ancestry Group, Analysis of Variance, Anti-HIV Agents, CD4 Lymphocyte Count, Cohort Studies, Ethnic Groups, Gene Frequency, Genealogy and Heraldry, Genotype, HIV Infections, Humans, Pharmacogenetics, South Africa
Citation
Journal of Human Genetics
54
5
54
5