Format

Send to

Choose Destination
Environ Res. 2015 Jul;140:95-101. doi: 10.1016/j.envres.2015.03.022. Epub 2015 Apr 2.

Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample.

Author information

1
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. Electronic address: esther.ng@well.ox.ac.uk.
2
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
3
Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
4
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
5
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
6
MTM Research Centre, Örebro University, 701 82 Örebro, Sweden.
7
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
8
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden. Electronic address: lars.lind@medsci.uu.se.

Abstract

BACKGROUND:

Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level.

OBJECTIVES:

Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs.

METHODS:

Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography-high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model.

RESULTS:

Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7×10(-13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8×10(-12)) for PCB-118, rs4802104 (p=1.4×10(-9)) for PCB-74 and rs4803413 (p=2.5×10(-9)) for PCB-105, all of which map to CYP2B6.

CONCLUSIONS:

In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity.

KEYWORDS:

Cytochrome P450; Genome-wide association studies; Metabolism; Pollutants; Polychlorinated biphenyls; Single nucleotide polymorphisms

PMID:
25839716
PMCID:
PMC4509719
DOI:
10.1016/j.envres.2015.03.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center