Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort.

The Journal of Antimicrobial Chemotherapy
Daniel F CarrClaudia P Cortes

Abstract

Efavirenz is extensively metabolized by CYP2B6, and associations between CYP2B6 polymorphisms and plasma efavirenz exposure have been reported. The objective of this study was to investigate CYP2B6 haplotype structure and functional consequences in a Latin American population. Two hundred and nineteen patients were recruited at Fundación Arriarán, Chile, between September and December 2008. Plasma efavirenz concentrations were determined using liquid chromatography with mass spectrometry. Genotyping for 30 single nucleotide polymorphisms (SNPs) with a minor allele frequency of >0.05 in the HapMap CEU population at intervals of approximately 1 kb across the CYP2B6 locus was conducted using Sequenom iPLEX MALDI-TOF. Thirteen SNPs passed quality control and, of these, statistically significant associations (P < 0.001) with plasma efavirenz concentrations were observed for 11. Pairwise tagging SNP analysis (R(2) > 0.8) identified 3 SNPs (rs10403955, rs2279345 and rs8192719) representative of the 11 associated SNPs. A composite genetic model of these three alleles was constructed, and an association between carriers of four to six of these alleles and the risk of efavirenz plasma concentrations >4 microg/mL was identified with an od...Continue Reading

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Citations

Sep 3, 2011·Pharmacogenetics and Genomics·Juan Gonzalo RestrepoJosé A G Agúndez
Feb 13, 2013·Drug Metabolism and Pharmacokinetics·Chonlaphat SukasemWeerawat Manosuthi
Dec 12, 2012·Pharmacogenomics and Personalized Medicine·Rebecca Pavlos, Elizabeth J Phillips
Jun 19, 2014·Expert Opinion on Drug Metabolism & Toxicology·Pablo BarreiroVincent Soriano
Apr 5, 2012·British Journal of Clinical Pharmacology·Chonlaphat SukasemWasun Chantratita
Jul 24, 2015·The Journal of Antimicrobial Chemotherapy·Nadezda ApostolovaJuan V Esplugues
Nov 29, 2017·The AAPS Journal·Volker M LauschkeMagnus Ingelman-Sundberg
May 19, 2018·Expert Opinion on Drug Metabolism & Toxicology·Gabriel StillemansLaure Elens
Mar 14, 2019·Molecular Genetics & Genomic Medicine·HariOm SinghRaman R Gangakhedkar
Jan 7, 2020·Mass Spectrometry Reviews·Jia-Jia CuiJi-Ye Yin
Apr 7, 2021·Drug Metabolism Reviews·Laura E RussellVolker M Lauschke
May 1, 2021·Cells·Laura CheneyJoan W Berman

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