title: Genetic variation in the CYP2B6 gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study.
abstract: 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 = 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.
  
  
  CONCLUSIONS
  Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.
authors.forename: Johanna
authors.initials: J
authors.lastname: Penell
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Tove
authors.initials: T
authors.lastname: Fall
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: Tomas
authors.initials: T
authors.lastname: Axelsson
authors.forename: Per
authors.initials: P
authors.lastname: Lundmark
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindgren
authors.forename: Anubha
authors.initials: A
authors.lastname: Mahajan
authors.forename: Samira
authors.initials: S
authors.lastname: Salihovic
authors.forename: Bert
authors.initials: B
authors.lastname: van Bavel
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.affiliation: Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden. Monica.Lind@medsci.uu.se.
authors.forename: P Monica
authors.initials: PM
authors.lastname: Lind
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000097:blood*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013548:Sweden
chemical_list: D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D008055:Lipids; C511295:2,2',4,4'-tetrabromodiphenyl ether; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6