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Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2014 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 133, 135-140 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2014. Vol. 133, 135-140 p.
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Environmental Health and Occupational Health
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URN: urn:nbn:se:uu:diva-226576DOI: 10.1016/j.envres.2014.05.017ISI: 000339705900018PubMedID: 24926919OAI: oai:DiVA.org:uu-226576DiVA: diva2:726463
Available from: 2014-06-18 Created: 2014-06-18 Last updated: 2017-12-05Bibliographically approved

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Lind, LarsPenell, JohannaSyvänen, Ann-ChristineAxelsson, TomasIngelsson, ErikLind, P Monica

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Lind, LarsPenell, JohannaSyvänen, Ann-ChristineAxelsson, TomasIngelsson, ErikLind, P Monica
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Cardiovascular epidemiologyOccupational and Environmental MedicineMolecular MedicineScience for Life Laboratory, SciLifeLabMolecular epidemiology
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