Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7

Details

Serval ID
serval:BIB_01BE917E653A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7
Journal
Pharmacogenetics and Genomics
Author(s)
Rotger  M., Saumoy  M., Zhang  K., Flepp  M., Sahli  R., Decosterd  L., Telenti  A.
ISSN
1744-6872 (Print)
Publication state
Published
Issued date
10/2007
Volume
17
Number
10
Pages
885-90
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Abstract
OBJECTIVE: To evaluate the possibility of copy number variation (CNV) of CYP2B6. METHODS: We investigated CNV in 226 HIV-1-infected individuals by quantitative PCR. Identification of a candidate CNV prompted characterization of the size of deletion by assessment of absence of exons, mapping of the recombination site by sequencing, and by southern blot. The functional consequences of CNV were assessed in silico (predicted protein), and in vivo, by evaluation of plasma drug levels of the CYP2B6 substrate efavirenz. RESULTS: Analyses identified one white individual carrying a heterozygous deletion of exons 1-4 of CYP2B6. We identified a approximately 68 kb deletion between CYP2B7 and CYP2B6, and mapped the crossover to a homologous region in intron 4 of both genes. The new hybrid allele, named CYP2B6*29, carries two amino acid substitutions, Q172H and M198T, previously associated with impaired enzyme function. Consistent with the functional prediction, the average of efavirenz area under the curve values of the patient was mean+/-SD, 81.64+/-23.62, versus 47.75+/-19.73 mug h/ml for individuals with an extensive metabolizer phenotype. CONCLUSION: CYP2B6*29 represents a new mechanism of genetic variation at the CYP2B6 locus, underscoring the highly polymorphic nature of this isoenzyme.
Pubmed
Web of science
Create date
25/01/2008 10:51
Last modification date
20/08/2019 12:23
Usage data