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

dc.contributor.advisorWarnich, L.
dc.contributor.advisorHillermann-Rebello, R.
dc.contributor.authorParathyras, John Burnsen_ZA
dc.contributor.otherUniversity of Stellenbosch. Faculty of Agrisciences. Dept. of Genetics.
dc.date.accessioned2008-01-16T09:43:08Zen_ZA
dc.date.accessioned2010-06-01T08:54:13Z
dc.date.available2008-01-16T09:43:08Zen_ZA
dc.date.available2010-06-01T08:54:13Z
dc.date.issued2007-03en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/2638
dc.descriptionThesis (MSc (Genetics))--University of Stellenbosch, 2007.
dc.description.abstractThe 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.extent2438770 bytesen_ZA
dc.format.mimetypeapplication/pdfen_ZA
dc.language.isoenen_ZA
dc.publisherStellenbosch : University of Stellenbosch
dc.subjectDissertations -- Geneticsen
dc.subjectTheses -- Geneticsen
dc.subjectAIDS (Disease) -- South Africaen
dc.subjectAntiretroviral agents -- South Africaen
dc.subjectPharmacogenetics -- South Africaen
dc.subjectHIV infections -- Treatment -- South Africaen
dc.subjectHIV infections -- South Africa -- Genetic aspectsen
dc.titleMolecular genetic analysis of human immunodeficiency virus antiretroviral therapy response in South Africa : a pharmacogenetics studyen_ZA
dc.typeThesisen_ZA
dc.rights.holderUniversity of Stellenbosch


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