skip to main content

SciTech ConnectSciTech Connect

Title: Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample

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, PCB169more » 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. - Highlights: • We studied the relationship between PCBs and the genetic variation in the CYP genes. • Cross sectional data from a cohort of elderly were analysed. • The PCB levels were evaluated versus 21 SNPs in three CYP genes. • PCB 118 was related to variation in the CYP1A1 gene.« less
Authors:
 [1] ;  [2] ; ;  [3] ;  [4] ;  [5] ; ;  [6] ; ;  [7] ;  [2]
  1. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala (Sweden)
  2. Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala (Sweden)
  3. Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala (Sweden)
  4. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala (Sweden)
  5. (United Kingdom)
  6. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford (United Kingdom)
  7. MTM Research Centre, School of Science and Technology, Örebro University, Örebro (Sweden)
Publication Date:
OSTI Identifier:
22447534
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environmental Research; Journal Volume: 133; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADMINISTRATIVE PROCEDURES; CAPTURE; CHROMATOGRAPHY; COST; DATA; DIOXIN; ECONOMICS; ELDERLY PEOPLE; ENZYMES; EPIDEMIOLOGY; GENES; GENOTYPE; HYDROCARBONS; MASS SPECTROSCOPY; METABOLISM; POLYCHLORINATED BIPHENYLS; RECEPTORS; RESOLUTION; SOCIO-ECONOMIC FACTORS; TESTING; VARIATIONS