Effects of CYP2B6 and CYP1A2 Genetic Variation on Nevirapine Plasma Concentration and Pharmacodynamics as Measured by CD4 Cell Count in Zimbabwean HIV-Infected Patients

Omics : a Journal of Integrative Biology
Doreen MhandireCollet Dandara

Abstract

The extremely high prevalence of HIV/AIDS in sub-Saharan Africa and limitations of current antiretroviral medicines demand new tools to optimize therapy such as pharmacogenomics for person-to-person variations. African populations exhibit greater genetic diversity than other world populations, thus making it difficult to extrapolate findings from one population to another. Nevirapine, an antiretroviral medicine, displays large plasma concentration variability which adversely impacts therapeutic virological response. This study, therefore, aimed to identify sources of variability in nevirapine pharmacokinetics and pharmacodynamics, focusing on genetic variation in CYP2B6 and CYP1A2. Using a cross-sectional study design, 118 HIV-infected adult Zimbabwean patients on nevirapine-containing highly active antiretroviral therapy (HAART) were characterized for three key functional single nucleotide polymorphisms (SNPs), CYP2B6 c.516G>T (rs3745274), CYP2B6 c.983T>C (rs28399499), and CYP1A2 g.-163C>A (rs762551). We investigated whether genotypes at these loci were associated with nevirapine plasma concentration, a therapeutic biomarker, and CD4 cell count, a biomarker of disease progression. CYP2B6 and CYP1A2 were chosen as the candidate...Continue Reading

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Citations

Sep 15, 2016·Omics : a Journal of Integrative Biology·Collen MasimirembwaPeter Derek Christian Leutscher
Oct 26, 2016·The Pharmacogenomics Journal·J L BakerC N Rotimi
May 19, 2018·Expert Opinion on Drug Metabolism & Toxicology·Gabriel StillemansLaure Elens
Jun 30, 2019·World Journal of Gastroenterology : WJG·Alaattin Sen, Holger Stark
Mar 1, 2016·Personalized Medicine·María Jesús Hernández ArroyoAlfonso Domínguez-Gil Hurlé
Aug 28, 2019·Pharmacogenomics·Oluseye O BolajiBabatunde A Adeagbo
Mar 25, 2021·Pharmacogenomics and Personalized Medicine·Monkgomotsi J MasengGiacomo M Paganotti

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Methods Mentioned

BETA
genotyping
PCR
electrophoresis

Software Mentioned

GeneMapper©
R Language and Environment for Statistical Computing ( R Core ...

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