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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians
Pharmacogenomics, Volume 13, No. 1, Year 2012
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Description
Aim: Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians. Materials & methods: CYP450 2B6, 2D6, 3A4 and 3A5, ABCB1 and constitutive androstane receptor and pregnane X receptor, were analyzed for polymorphisms in 26 subjects. Results: Allele frequencies (variant) were: CYP2B6 514G>T (0.31) CYP2D6*4 (0.02); CYP2D6*17 (0.35); CYP3A4*1B (0.77); CYP3A5*3 (0.25); ABCB1 2677G>T (0.0), ABCB1 3435C>T (0.21), NR1I3 13711152T>C (0.02), NR1I2 44477T>C (0.10), NR1I2 63396C>T (0.33), NR1I2 6-bp indel (del: 0.17). CYP2B6 516G>T (non-wild-type/wild-type) correlated with nevirapine pharmacokinetic parameters; geometric mean ratios (95% CI): 1.75 (1.27-2.40) for area under the concentration time curve (AUC) 0-12 h, 1.58 (1.03-2.42) for C 0, and 0.53 (0.31-0.91) for clearance. In a multivariable model, nevirapine AUC increased by 1.5% per year of age (p < 0.0001), CYP2B6 516 T allele increased AUC by 92% (p < 0.0001), and CYP3A5*3 decreased AUC by 31% (p = 0.0027). Conclusion: Allele frequencies were similar to other sub-Saharan African populations. The T allele for CYP2B6 516 was significantly associated with nevirapine exposure. Original submitted 15 June 2010; Revision submitted 5 July 201. © 2012 Future Medicine Ltd.
Authors & Co-Authors
Brown, Kevin C.
United States, Chapel Hill
Unc Eshelman School of Pharmacy
Hosseinipour, Mina C.
United States, Chapel Hill
Unc School of Medicine
Hoskins, Janelle M.
United States, Chapel Hill
Unc Eshelman School of Pharmacy
Thirumaran, Ranjit K.
United States, Memphis
St. Jude Children's Research Hospital
Tien, Hsiaochuan
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Weigel, Ralf
United States, Memphis
St. Jude Children's Research Hospital
Tauzie, Jean
United States, Minneapolis
College of Pharmacy
Shumba, Idah
Malawi, Lilongwe
Lighthouse Trust
Lamba, Jatinder Kaur
Malawi, Lilongwe
Lighthouse Trust
Schuetz, Erin G.
United States, Chapel Hill
Unc School of Medicine
McLeod, Howard Lewis
United States, Chapel Hill
Unc School of Medicine
Kashuba, Angela D.M.
United States, Chapel Hill
Unc School of Medicine
Corbett, Amanda H.
United States, Chapel Hill
Unc Eshelman School of Pharmacy
Statistics
Citations: 36
Authors: 13
Affiliations: 6
Identifiers
Doi:
10.2217/pgs.11.132
ISSN:
14622416
e-ISSN:
17448042
Research Areas
Genetics And Genomics
Health System And Policy