Exposure to polybrominated biphenyl (PBB) associates with DNA methylation differences across the genome
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PROVIDER: PRJNA478257 | ENA |
REPOSITORIES: ENA
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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:Genetic Predictors of Polybrominated biphenyl (PBB) Elimination
| PRJNA553008 | ENA
Project description:Genetic Predictors of Polybrominated biphenyl (PBB) Elimination
| PRJNA553007 | ENA
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: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: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:BackgroundBrominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973-1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function.MethodsIn 2004-2006, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine samples for up to 6 months. We assayed the urine samples for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35-42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973-1974 (n = 70).ResultsWe observed that high (>3.0 parts per billion [ppb]) and medium (>1.0-3.0 ppb) PBB exposure were associated with lower E13G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (≤1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure.ConclusionOur results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.
| S-EPMC6679744 | biostudies-literature
Project description:Endocrine-disrupting compounds are associated with altered epigenetic regulation and adverse health outcomes, although inconsistent results suggest that people have varied responses to the same exposure. Interpersonal variation in response to environmental exposures is not identified using standard, population-based methods. However, methods that capture an individual's response, such as analyzing stochastic epigenetic mutations (SEMs), may capture currently missed effects of environmental exposure. To test whether polybrominated biphenyl (PBB) was associated with SEMs, DNA methylation was measured using Illumina's MethylationEPIC array in PBB-exposed individuals, and SEMs were identified. Association was tested using a linear regression with robust sandwich variance estimators, controlling for age, sex, lipids, and cell types. The number of SEMs was variable (range: 119-18,309), and positively associated with age (p = 1.23e-17), but not with sex (p = 0.97). PBBs and SEMs were only positively associated in people who were older when they were exposed (p = 0.02 vs. p = 0.91). Many subjects had SEMs enriched in biological pathways, particularly in pathways involved with xenobiotic metabolism and endocrine function. Higher number of SEMs was also associated with higher age acceleration (intrinsic: p = 1.70e-3; extrinsic: p = 3.59e-11), indicating that SEMs may be associated with age-related health problems. Finding an association between environmental contaminants and higher SEMs may provide insight into individual differences in response to environmental contaminants, as well as into the biological mechanism behind SEM formation. Furthermore, these results suggest that people may be particularly vulnerable to epigenetic dysregulation from environmental exposures as they age.
| S-EPMC6691996 | biostudies-literature
Project description:Polybrominated diphenyl ethers (PBDEs)
| PRJNA489665 | ENA
Project description:In 1973-74, a polybrominated biphenyl (PBB) flame retardant mixture was shipped to Michigan livestock feed mills in place of a nutritional supplement and contaminated the food supply. Following the accident, the Michigan PBB Registry was established to study the long-term health effects of halogenated compounds and is now led by a community-academic partnership. PBB exposure is associated with altered DNA methylation in sperm, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB). Paternal PBB and PCB levels of men enrolled in the Michigan PBB Registry (n = 155) were analyzed against matched offspring birthweight and gestational age (n = 336). Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks, respectively, and paternal PBB and PCB levels were examined as continuous measures and divided into tertiles. Associations of offspring birthweight and gestational age with paternal PBB and PCB serum concentrations were modeled using multivariable linear spline and log-risk regression, adjusting for family clustering, paternal health and lifestyle factors, maternal PBB, and PCB serum concentrations, sex, and offspring gestational age (for birthweight). Fathers in the middle and upper PBB and PCB tertiles had increased risks for lowest quartile birthweight compared to the first tertile, with adjusted risk ratios (aRR) = 1.67 (95% CI: 0.93, 2.99) and aRR = 2.06 (95% CI: 1.12, 3.79) for PBB, and aRR = 1.47 (95% CI: 0.79, 2.75) and aRR = 1.34 (95% CI: 0.70, 2.54) for PCB, respectively. Elevated paternal PBB levels were not associated with an increased risk for preterm birth, while PCB levels were associated with a small, but not significant, decrease in gestational age, β = -0.37 (95% CI: -0.76, 0.03) weeks per log unit increase PCB. The findings suggest that increased paternal PBB and PCB levels negatively impact offspring birthweight, and paternal PCB levels may negatively impact gestational age.
| S-EPMC9930206 | biostudies-literature