Document Detail


A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups.
MedLine Citation:
PMID:  19282874     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (P=0.03) and G2677A (P<0.01) 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.
Authors:
John Parathyras; Stefan Gebhardt; Renate Hillermann-Rebello; Nelis Grobbelaar; Mauritz Venter; Louise Warnich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-13
Journal Detail:
Title:  Journal of human genetics     Volume:  54     ISSN:  1435-232X     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-25     Completed Date:  2010-02-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  261-5     Citation Subset:  IM    
Affiliation:
Department of Genetics, Stellenbosch University, Private Bag X1, Matieland, South Africa.
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MeSH Terms
Descriptor/Qualifier:
African Continental Ancestry Group / genetics
Analysis of Variance
Anti-HIV Agents / therapeutic use*
CD4 Lymphocyte Count*
Cohort Studies
Ethnic Groups / genetics*
Gene Frequency
Genealogy and Heraldry
Genotype
HIV Infections / drug therapy*,  genetics*
Humans
Pharmacogenetics*
South Africa
Chemical
Reg. No./Substance:
0/Anti-HIV Agents

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