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

Background: 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. Methods: In 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). Results: Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P =1 0 −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. Conclusion: Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.