Molecular genetic analysis of human immunodeficiency virus antiretroviral therapy response in South Africa : a pharmacogenetics study

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dc.contributor.advisor Warnich, L.
dc.contributor.advisor Hillermann-Rebello, R. Parathyras, John Burns en_ZA
dc.contributor.other University of Stellenbosch. Faculty of Agrisciences. Dept. of Genetics. 2008-01-16T09:43:08Z en_ZA 2010-06-01T08:54:13Z 2008-01-16T09:43:08Z en_ZA 2010-06-01T08:54:13Z 2007-03 en_ZA
dc.description Thesis (MSc (Genetics))--University of Stellenbosch, 2007.
dc.description.abstract The results of pharmacotherapy can vary both within and between different populations and ethnic groups. Although numerous factors are believed responsible for observed discrepancies in drug response, genetic differences, most often in the form of single nucleotide polymorphisms (SNPs), between individuals and ethnic groups are an important and at times predominant factor. The response to antiretroviral (ARV) drugs for the treatment of human immunodeficiency virus (HIV)-infection is not dissimilar. Marked variations in both ARV efficacy and occurrence of adverse drug reactions (ADRs) have been observed on both an individual and ethnic group level, which are largely attributed to polymorphisms within genes involved in the metabolism and transport of these compounds – such genes include the CYP2B6 and CYP3A4 genes, both members of the cytochrome P450 (CYP) gene superfamily, and the multidrug-resistance 1 (MDR1) gene encoding an efflux transporter protein, phosphoglycoprotein (PGP). An improved understanding of the genetic influences on ARV drug response could lead to improved therapies with fewer side-effects and minimised drug resistance. The main aim of this study was thus to investigate the genetic basis of observed differences in ARV therapy (ART) response in South African ethnic groups. Deoxyribonucleic acid (DNA) samples were collected from 206 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity that were currently or prospectively receiving ART. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was employed to screen the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in MDR1. Hardy-Weinberg equilibrium (HWE) and haplotype analyses were subsequently performed on the resultant SNP genotype and ... en_ZA
dc.format.extent 2438770 bytes en_ZA
dc.format.mimetype application/pdf en_ZA
dc.language.iso en en_ZA
dc.publisher Stellenbosch : University of Stellenbosch
dc.subject Dissertations -- Genetics en
dc.subject Theses -- Genetics en
dc.subject AIDS (Disease) -- South Africa en
dc.subject Antiretroviral agents -- South Africa en
dc.subject Pharmacogenetics -- South Africa en
dc.subject HIV infections -- Treatment -- South Africa en
dc.subject HIV infections -- South Africa -- Genetic aspects en
dc.title Molecular genetic analysis of human immunodeficiency virus antiretroviral therapy response in South Africa : a pharmacogenetics study en_ZA
dc.type Thesis en_ZA
dc.rights.holder University of Stellenbosch
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