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Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.ORCID iD: 0000-0002-8949-3555
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2015 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 140, 95-101 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 140, 95-101 p.
Keyword [en]
Genome-wide association studies, Polychlorinated biphenyls, Cytochrome P450, Single nucleotide polymorphisms, Metabolism, Pollutants
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-252373DOI: 10.1016/j.envres.2015.03.022ISI: 000357904100011PubMedID: 25839716OAI: oai:DiVA.org:uu-252373DiVA: diva2:810087
Funder
Wellcome trust, WT098017 WT090532 097306/Z/11/Z WT064890
Note

Esther Ng and Samira Salihovic contributed equally to the manuscript.

Available from: 2015-05-06 Created: 2015-05-06 Last updated: 2017-12-04Bibliographically approved

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Salihovic, SamiraLind, P. MonicaSyvänen, Ann-ChristineAxelsson, TomasIngelsson, ErikLind, Lars

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