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

Abstract

Objectives: 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. Patients and methods: 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 ~1 kb across the CYP2B6 locus was conducted using Sequenom iPLEX MALDI-TOF. Results: 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 (R2>.0.8) identified 3 SNPs (rs10403955, rs2279345 and r