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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.

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

SUBMITTER: Ng E

PROVIDER: S-EPMC4509719 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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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.

Ng Esther E Salihovic Samira S Lind P Monica PM Mahajan Anubha A Syvänen Anne-Christine AC Axelsson Tomas T Ingelsson Erik E Lindgren Cecilia M CM van Bavel Bert B Morris Andrew P AP Lind Lars L

Environmental research 20150402

<h4>Background</h4>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.<h4>Objectives</h4>Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs.<h4>Methods</h4>Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Swe ...[more]

PMID: 25839716

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Project description:Concern persists over endocrine-disrupting effects of persistent organic pollutants (POPs) on human growth and sexual maturation. Potential effects of toxicant exposures on testosterone levels during puberty are not well characterized.In this study we evaluated the relationship between toxicants [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p´-DDE), hexachlorobenzene (HCB), and lead] and testosterone levels among 127 Akwesasne Mohawk males 10 to < 17 years of age with documented toxicant exposures.Data were collected between February 1996 and January 2000. Fasting blood specimens were collected before breakfast by trained Akwesasne Mohawk staff. Multivariable regression models were used to estimates associations between toxicants and serum testosterone, adjusted for other toxicants, Tanner stage, and potential confounders.The sum of 16 PCB congeners (?16PCBs) that were detected in ? 50% of the population was significantly and negatively associated with serum testosterone levels, such that a 10% change in exposure was associated with a 5.6% decrease in testosterone (95% CI: -10.8, -0.5%). Of the 16 congeners, the more persistent ones (?8PerPCBs) were related to testosterone, whereas the less persistent ones, possibly reflecting more recent exposure, were not. When PCB congeners were subgrouped, the association was significant for the sum of eight more persistent PCBs (5.7% decrease; 95% CI: -11, -0.4%), and stronger than the sum of six less persistent congeners (3.1% decrease; 95% CI: -7.2, 0.9%). p,p´-DDE was positively but not significantly associated with serum testosterone (5.2% increase with a 10% increase in exposure; 95% CI: -0.5, 10.9%). Neither lead nor HCB was significantly associated with testosterone levels.Exposure to PCBs, particularly the more highly persistent congeners, may negatively influence testosterone levels among adolescent males. The positive relationship between p,p´-DDE and testosterone indicates that not all POPs act similarly.Schell LM, Gallo MV, Deane GD, Nelder KR, DeCaprio AP, Jacobs A; Akwesasne Task Force on the Environment. 2014. Relationships of polychlorinated biphenyls and dichlorodiphenyldichloroethylene (p,p´-DDE) with testosterone levels in adolescent males. Environ Health Perspect 122:304-309;?http://dx.doi.org/10.1289/ehp.1205984.

Dataset Information

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

Publications

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

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