Pyrosequencing-based screening for genetic polymorphisms in cytochrome P450 2B6 of potential clinical relevance.

Abstract:

OBJECTIVES:Three exonic single nucleotide polymorphisms (SNPs) in the cytochrome P450 2B6 (CYP2B6) gene, 516G>T, 785A>G and 1459C>T, have been described to be associated with functional changes in the CYP2B6 catalytic activity or protein expression. They are therefore of potential clinical importance for drug efficacy and safety of CYP2B6 substrates, in particular of antiretroviral therapy regimes that include efavirenz. Therefore, we aimed at providing genetic screening assays for these three SNPs. METHODS:Simplex Pyrosequencing assays were developed for the selected CYP2B6 SNPs. A total of 273 DNA samples from healthy volunteers of Caucasian ethnicity were genotyped. RESULTS:The presently developed Pyrosequencing assays afford an accurate determination of the three SNPs in the 273 DNA samples. The assays were verified by routine implementation of control samples obtained by conventional sequencing. The frequencies for the variant alleles 516T, 785G and 1459T were 0.22, 0.24 and 0.13, respectively. All genotype frequencies were in agreement with the Hardy-Weinberg equilibrium. CYP2B6 alleles CYP2B6*5A (1459T), CYP2B6*6 (516T/785G) and *7B (516T/785G/1459T) were found at allelic frequencies of 0.12, 0.20 and 0.01. CONCLUSION:The present reliable and quick Pyrosequencing assays afford facilitating future research on the importance of CYP2B6 pharmacogenetics for personalized drug therapy with CYP2B6 substrates.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Rohrbacher M,Kirchhof A,Geisslinger G,Lötsch J

doi

10.2217/14622416.7.7.995

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

995-1002

issue

7

eissn

1462-2416

issn

1744-8042

journal_volume

7

pub_type

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