Genetic variation in the CYP2B6 gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study.

Johanna Penell,Anubha Mahajan,Andrew P Morris,Tomas Axelsson,P Monica Lind,Samira Salihovic,Erik Ingelsson,Tove Fall,Bert Van Bavel,Anne-Christine Syvänen,Lars Lind,Cecilia Lindgren,Per Lundmark

doi:10.1186/1476-069x-13-34

Abstract

BackgroundSince human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample.MethodsIn the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS).ResultsSeveral SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10-4 to 10-9). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals.ConclusionCirculating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.

Highlights

Since human cytochrome P450 2B6 (CYP2B6) has been identified as the major cytochrome P450 (CYP) enzyme involved in the metabolism of 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample
Considering the severe adverse health effects reported in relation to Polybrominated diphenyl ethers (PBDEs) concentrations, it is of outmost importance to increase the understanding of PBDE metabolism. 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) is the most commonly detected PBDE congener in human serum worldwide [8,9,10,11,12,13]
This study investigated whether the experimental findings on the associations between single nucleotide polymorphisms (SNPs) in CYP2B6 regarding BDE-47 concentrations could be repeated in an epidemiological cross-sectional observational study in humans

Summary

Introduction

Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample. The use of certain PBDEs has been restricted or banned in the European Union since 2004. Due to their been reported [7]. We have previously reported concentrations of BDE-47 in the majority of elderly men and women in a population-based sample [14]. We use this congener as a marker for PBDE exposure as it is frequently detected and included in a large number of biomonitoring studies and valid for comparison

Methods

Results

Discussion

Conclusion