Genetic Predictors of Polybrominated biphenyl (PBB) Elimination
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PROVIDER: PRJNA553007 | ENA |
REPOSITORIES: ENA
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Project description:Genetic Predictors of Polybrominated biphenyl (PBB) Elimination
| PRJNA553008 | ENA
Project description:Polybrominated biphenyl (PBB) is an endocrine-disrupting compound which was accidently added to the food supply in Michigan in the 1970’s. Highly exposed individuals and their children have numerous health problems, though the underlying mechanism behind these health problems remains unknown. Other endocrine-disrupting compounds have been linked to epigenetic differences, but no epigenetic studies have been done for PBB. In this study, DNA from the blood of individuals with PBB exposure from the Michigan PBB Registry was interrogated with the MethylationEPIC BeadChip (N = 659). Associations between each of the ~850,000 CpG sites and current, serum PBB levels were tested with a linear regression that controlled for age, sex, and cell type proportions. We show that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways.
2018-08-01 | GSE116339 | GEO
Project description:Exposure to polybrominated biphenyl (PBB) associates with DNA methylation differences across the genome
| PRJNA478257 | ENA
Project description:Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
| S-EPMC6710070 | biostudies-literature
Project description:In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBB-associated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways.
| S-EPMC6380401 | biostudies-literature
Project description:BackgroundPolybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes.ObjectivesIn this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry.MethodsHRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and ΣPCB (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow.ResultsMean levels were 1.75 ng/mL [standard deviation (SD): 13.9] for PBB-153 and 1.04 ng/mL (SD: 0.788) for ΣPCB. Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) p<0.2], respectively. There were 2,861 features associated with ΣPCB (FDR p<0.2). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with ΣPCB in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with ΣPCB levels (level 1 evidence).ConclusionsOur results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that ΣPCB was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657.
| S-EPMC10564108 | biostudies-literature
Project description:Polybrominated diphenyl ethers (PBDEs)
| PRJNA489665 | ENA
Project description:Transcriptomic analysis of the cells grown on biphenyl in the sterilized soil and those grown on biphenyl to mid-exponential phase in a liquid medium
2010-06-10 | GSE22240 | GEO
Project description:two cultures one grown on biphenyl and other on pyruvate Keywords: growth type
2006-11-01 | GSE5268 | GEO
Project description:protein based stable isotope probing was performed for identifying microorganisms actually responsible for biphenyl biodegradation in soil environment.
2022-02-16 | PXD023646 | Pride