title: Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample.
abstract: Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures >80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003-0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005-0.05 range. Very few associations with p<0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs.
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Penell
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Axelsson
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindgren
authors.affiliation: MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
authors.forename: Samira
authors.initials: S
authors.lastname: Salihovic
authors.affiliation: MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
authors.forename: Bert
authors.initials: B
authors.lastname: van Bavel
authors.affiliation: Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden. Electronic address: monica.lind@medsci.uu.se.
authors.forename: P Monica
authors.initials: PM
authors.lastname: Lind
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics*; D003430:Cross-Sectional Studies; D019363:Cytochrome P-450 CYP1A1 / Q000097:blood / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000097:blood / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D011078:Polychlorinated Biphenyls / Q000097:blood*; D020641:Polymorphism, Single Nucleotide
chemical_list: C070055:2,3',4,4',5-pentachlorobiphenyl; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1
keywords: CYP; Epidemiology; Gene; Metabolism; PCB; SNP