Andrea Baccarelli

Harvard University, Cambridge, Massachusetts, United States

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Publications (282)1354.68 Total impact

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    Andrea A Baccarelli, Hyang-Min Byun
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    ABSTRACT: Platelets are critical in the etiology of cardiovascular disease (CVD), and the mitochondria in these cells serve as an energy source for platelet function. Epigenetic factors, especially DNA methylation, have been employed as markers of CVD. Unlike nuclear DNA methylation, mitochondrial DNA (mtDNA) methylation has not been widely studied, in part, due to debate about its existence and role. In this study, we examined platelet mtDNA methylation in relation to CVD. We measured mtDNA methylation in platelets by bisulfite-PCR pyrosequencing and examined associations of CVD with methylation in mitochondrial genes; cytochrome c oxidase (MT-CO1, MT-CO2, and MT-CO3); tRNA leucine 1 (MT-TL1); ATP synthase (MT-ATP6 and MT-ATP8); and NADH dehydrogenase (MT-MD5). We report that CVD patients have significantly higher mtDNA methylation than healthy controls in MT-CO1 (18.53%, P < 0.0001), MT-CO2 (3.33%, P = 0.0001), MT-CO3 (0.92%, P < 0.0001), and MT-TL1 (1.67%, P = 0.0001), which are involved in ATP synthesis. Platelet mtDNA methylation was not related with age, BMI, and race in this study. Our results suggest that platelet mtDNA methylation, which could serve as non-invasive and easy-to-obtain markers, may be implicated in the etiology of CVD.
    Clinical Epigenetics 12/2015; 7(1). DOI:10.1186/s13148-015-0078-0 · 6.22 Impact Factor
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    ABSTRACT: Recent advances in estimating fine particle (PM2.5) ambient concentrations use daily satellite measurements of aerosol optical depth (AOD) for spatially and temporally resolved exposure estimates. Mexico City is a dense megacity that differs from other previously modeled regions in several ways: it has bright land surfaces, a distinctive climatological cycle, and an elevated semi-enclosed air basin with a unique planetary boundary layer dynamic. We extend our previous satellite methodology to the Mexico City area, a region with higher PM2.5 than most US and European urban areas. Using a novel 1 km resolution AOD product from the MODIS instrument, we constructed daily predictions across the greater Mexico City area for 2004-2014. We calibrated the association of AOD to PM2.5 daily using municipal ground monitors, land use, and meteorological features. Predictions used spatial and temporal smoothing to estimate AOD when satellite data were missing. Our model performed well, resulting in an out-of-sample cross validation R2 of 0.724. Cross-validated root mean squared prediction error (RMSPE) of the model was 5.55 μg/m3. This novel model reconstructs long- and short-term spatially resolved exposure to PM2.5 for epidemiological studies in Mexico City.
    Environmental Science & Technology 06/2015; DOI:10.1021/acs.est.5b00859 · 5.48 Impact Factor
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    ABSTRACT: Recurrent, rapidly growing nasal polyps are hallmarks of aspirin-exacerbated respiratory disease (AERD), though the mechanisms of polyp growth have not been identified. Fibroblasts are intimately involved in tissue remodeling, and the growth of fibroblasts is suppressed by prostaglandin E2 (PGE2), which elicits antiproliferative effects mediated through the E Prostanoid (EP)2 receptor. We now report that cultured fibroblasts from the nasal polyps of subjects with AERD resist this antiproliferative effect. Fibroblasts from polyps of AERD subjects resisted the antiproliferative actions of PGE2 and a selective EP2 agonist (P<0.0001 at 1µM) compared with nasal fibroblasts from aspirin tolerant control subjects undergoing polypectomy or from healthy control subjects undergoing concha bullosa resections. Cell surface expression of the EP2 receptor protein was lower in fibroblasts from AERD subjects than in fibroblasts from healthy controls and aspirin-tolerant subjects (P<0.01 for both). Treatment of the fibroblasts with trichostatin A (TSA), a histone deacetylase inhibitor, significantly increased EP2 receptor mRNA in fibroblasts from AERD and aspirin-tolerant subjects, but had no effect on COX-2, EP4 and mPGES1 mRNA levels. Histone acetylation (H3K27ac) at the EP2 promoter correlated strongly with baseline EP2 mRNA (r=0.80, P<0.01). These studies suggest that the EP2 promotor is under epigenetic control and one explanation for PGE2 resistance in AERD is an epigenetically mediated reduction of EP2 receptor expression which could contribute to the refractory nasal polyposis typically observed in this syndrome.
    American Journal of Respiratory Cell and Molecular Biology 06/2015; DOI:10.1165/rcmb.2014-0486OC · 4.11 Impact Factor
  • The Journal of allergy and clinical immunology 05/2015; DOI:10.1016/j.jaci.2015.04.032 · 11.25 Impact Factor
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    ABSTRACT: Previous studies have reported epigenetic changes induced by environmental exposures. However, previous investigations did not distinguish 5-methylcytosine (5mC) from a similar oxidative form with opposite functions, 5-hydroxymethylcytosine (5hmC). Here, we measured blood DNA global 5mC and 5hmC by ELISA and used adjusted mixed-effects regression models to evaluate the effects of ambient PM10 and personal PM2.5 and its elemental components-black carbon (BC), aluminum (Al), calcium (Ca), potassium (K), iron (Fe), sulfur (S), silicon (Si), titanium (Ti), and zinc (Zn)-on blood global 5mC and 5hmC levels. The study was conducted in 60 truck drivers and 60 office workers in Beijing, China from The Beijing Truck Driver Air Pollution Study at two exams separated by one to two weeks. Blood 5hmC level (0.08%) was ˜83-fold lower than 5mC (6.61%). An inter-quartile range (IQR) increase in same-day PM10 was associated with increases in 5hmC of 26.1% in office workers (P=0.004), 20.2% in truck drivers (P=0.014), and 21.9% in all participants combined (P<0.001). PM10 effects on 5hmC were increasingly stronger when averaged over 4, 7, and 14 days preceding assessment (up to 132.6% for the 14-day average in all participants, P<0.001). PM10 effects were also significant after controlling for multiple testing (family-wise error rate; FWER<0.05). 5hmC was not correlated with personal measures of PM2.5 and elemental components (FWER>0.05). 5mC showed no correlations with PM10, PM2.5, and elemental components measures (FWER>0.05). Our study suggests that exposure to ambient PM10 affects 5hmC over time, but not 5mC. This finding demonstrates the need to differentiate 5hmC and 5mC in environmental studies of DNA methylation.
    Epigenetics: official journal of the DNA Methylation Society 05/2015; DOI:10.1080/15592294.2015.1050174 · 5.11 Impact Factor
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    ABSTRACT: Pulmonary embolism (PE) is the most serious manifestation of venous thromboembolism and a leading cause of sudden death. Several studies have suggested associations of venous thromboembolism with short-term particulate matter (PM) exposure; evidence on long-term PM and traffic exposure is mixed. We examined the association of long-term exposure to PM2.5, PM2.5-10 and PM10, and distance to roadways with overall incident PE and with PE subtypes in a cohort of US women. The study included 115,745 women from the Nurses' Health Study, followed from 1992-2008. Incident PE cases were self-reported biennially. Nonidiopathic PE were cases for which the medical record revealed an underlying health condition related to PE (i.e., surgery, trauma or malignancy); idiopathic PE were cases with no such history. We used spatiotemporal models combining spatial smoothing and geographic covariates to quantify exposure at residential addresses, and Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). PM2.5 averaged over 1 month (HR=1.22, 95% CI: 1.04, 1.44) or 12 months (HR=1.17, 95% CI: 0.93, 1.48) was associated with incident PE, after adjusting for known risk factors and PM2.5-10. Equivalent analyses restricted to PE subtypes showed a positive association for PM2.5 with nonidiopathic PE, but not with idiopathic PE. We did not find evidence of an association between distance to roadways and PE risk. We provide evidence that PM in the prior 1 and 12 months is associated with PE risk. Our results also suggest that women with underlying health conditions may be more susceptible to PE after PM exposure.
    Environmental Health Perspectives 05/2015; DOI:10.1289/ehp.1408927 · 7.03 Impact Factor
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    ABSTRACT: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increase CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86 +/- 7mg/m(3)) and 24 administrative workers (reference group, mean levels 0.21 +/- 0.02mg/m(3)) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-Pyrosequencing in order to measure methylation levels at promoter region of 13 genes. In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r=-.36, p<0.05), as well as for IL6 promoter methylation levels (r=.44, p<0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to non smokers (p=0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r=-.37, p<0.05 and r=-.34, p<0.05 respectively). These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. Copyright © 2015. Published by Elsevier Inc.
    Toxicology and Applied Pharmacology 05/2015; 286(3). DOI:10.1016/j.taap.2015.04.016 · 3.63 Impact Factor
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    ABSTRACT: Accelerated telomere shortening may cause cancer via chromosomal instability, making it a potentially useful biomarker. However, publications on blood telomere length (BTL) and cancer are inconsistent. We prospectively examined BTL measures over time and cancer incidence.
    04/2015; 63. DOI:10.1016/j.ebiom.2015.04.008
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    2015 New England Science Symposium, Joseph B. Martin Conference Center, Harvard Medical School; 04/2015
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    ABSTRACT: Air pollution has been related to mean changes in outcomes, including DNA methylation. However, mean regression analyses may not capture associations that occur primarily in the tails of the outcome distribution. This study examined whether the association between particulate air pollution and DNA methylation differs across quantiles of the methylation distribution. We focused on methylation of candidate genes related to coagulation and inflammation: coagulation factor III (F3), intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFN-γ), interleukin-6 (IL-6), and toll-like receptor 2 (TRL-2). We measured gene-specific blood DNA methylation repeatedly in 777 elderly men participating in the Normative Aging Study (1999-2010). We fit quantile regressions for longitudinal data to investigate whether the associations of particle number, PM2.5 black carbon, and PM2.5 mass concentrations (4-weeks moving average) with DNA methylation [expressed as the percentage of methylated cytosines over the sum of methylated and unmethylated cytosines at position 5 (%5mC)] varied across deciles of the methylation distribution. We reported the quantile regression coefficients which corresponded to absolute differences in DNA methylation (expressed in %5mC) associated with an interquartile range increase in air pollution concentration. Interquartile range increases in particle number, PM2.5 black carbon, and PM2.5 mass concentrations were associated with significantly lower methylation in the lower tails of the IFN-γ and ICAM-1 methylation distributions. For instance, a 3.4 µg/m(3) increase in PM2.5 mass concentration was associated with a 0.18%5mC (95% CI: -0.30, -0.06) decrease on the 20th percentile of ICAM-1 methylation, but was not significantly related to the 80th percentile (Estimate: 0.07%5mC, 95% CI: -0.09, 0.24). In our study population of older men, air pollution exposures were associated with a left shift in the lower tails of the IFN-γ and ICAM-1 methylation distributions.
    Environmental Health Perspectives 03/2015; DOI:10.1289/ehp.1307824 · 7.03 Impact Factor
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    ABSTRACT: BACKGROUND Single-nucleotide polymorphisms (SNPs) in inflammation, one-carbon metabolism, and skin cancer genes might influence susceptibility to arsenic-induced skin lesions.METHODSA case-control study was conducted in Pabna, Bangladesh (2001-2003), and the drinking-water arsenic concentration was measured for each participant. A panel of 25 candidate SNPs was analyzed in 540 cases and 400 controls. Logistic regression was used to estimate the association between each SNP and the potential for gene-environment interactions in the skin lesion risk, with adjustments for relevant covariates. Replication testing was conducted in an independent Bangladesh population with 488 cases and 2,794 controls.RESULTSIn the discovery population, genetic variants in the one-carbon metabolism genes phosphatidylethanolamine N-methyltransferase (rs2278952, P for interaction = .004; rs897453, P for interaction = .05) and dihydrofolate reductase (rs1650697, P for interaction = .02), the inflammation gene interleukin 10 (rs3024496, P for interaction = .04), and the skin cancer genes inositol polyphosphate-5-phosphatase (INPP5A; rs1133400, P for interaction = .03) and xeroderma pigmentosum complementation group C (rs2228000, P for interaction = .01) significantly modified the association between arsenic and skin lesions after adjustments for multiple comparisons. The significant gene-environment interaction between a SNP in the INPP5A gene (rs1133400) and water arsenic with respect to the skin lesion risk was successfully replicated in an independent population (P for interaction = .03).CONCLUSIONS Minor allele carriers of the skin cancer gene INPP5A modified the odds of arsenic-induced skin lesions in both main and replicative populations. Genetic variation in INPP5A appears to have a role in susceptibility to arsenic toxicity. Cancer 2015. © 2015 American Cancer Society.
    Cancer 03/2015; DOI:10.1002/cncr.29291 · 4.90 Impact Factor
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    ABSTRACT: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed. We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
    Environmental Health Perspectives 02/2015; DOI:10.1289/ehp.1409149 · 7.03 Impact Factor
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    ABSTRACT: Literature relating air pollution exposure to DVT and pulmonary embolism (PE), in spite of biological plausibility, is sparse. No comprehensive study examining associations between both short and long term exposure to Particulate matter (PM)2.5 and DVT or PE has been published to date. Using a novel PM2.5 prediction model we study whether long and short term PM2.5 exposure is associated with DVT and PE admissions among elderly across the northeastern USA. We estimated daily exposure of PM2.5 in each zipcode. We investigated long and short-term effects of PM2.5 on DVT and PE hospital admissions. There were 453,413 DVT and 151,829 PE admissions in the study. For short term exposure, we performed a case crossover analysis matching on month and year and defined the hazard period as lag 01 (exposure of day of admission and previous day). For the long term association, we used a Poisson regression. A 10-μg/m(3) increase in short term exposure was associated with a 0.63% increase in DVT admissions (95% CI = 0.03 to 1.25) and a 6.98% (95% CI = 5.65 to 8.33) increase in long term exposure admissions. For PE, the associated risks were 0.38 (95% CI = -0.68 to 1.25) and 2.67% (95% CI = 5.65 to 8.33). These results persisted when analyses were restricted to location-periods meeting the current EPA annual standard of 12-μg/m(3) . Our findings showed that PM2.5 exposure was associated with DVT and PE hospital admissions, and that current standards are not protective of this result. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 02/2015; 13(5). DOI:10.1111/jth.12873 · 5.55 Impact Factor
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    ABSTRACT: Epigenetic dysregulation in disease is increasingly studied as a potential mediator of pathophysiology. The epigenetic events are believed to occur in somatic cells, but the limited changes of DNA methylation in studies to date indicate that only subsets of the cells tested undergo epigenetic dysregulation. The recognition of this subpopulation effect indicates the need for care in design and execution of epigenome-wide association studies (EWASs), paying particular attention to confounding sources of variability. To maximize the sensitivity of the EWASs, ideally, the cell type mediating the disease should be tested, which is not always practical or ethical in human subjects. The value of using accessible cells as surrogates for the target, disease-mediating cell type has not been rigorously tested to date. In this review, participants in a workshop convened by the National Institutes of Health update EWAS design and execution guidelines to reflect new insights in the field.
    01/2015; 1. DOI:10.1016/j.nepig.2014.10.004
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    ABSTRACT: Background DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. Results Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43. Conclusions DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0584-6) contains supplementary material, which is available to authorized users.
    Genome Biology 01/2015; 16(1):25. DOI:10.1186/s13059-015-0584-6 · 10.47 Impact Factor
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    ABSTRACT: Short-term fine particles (PM2.5) exposure is associated with reduced heart rate variability, a strong predictor of cardiac mortality among older people. Identifying modifiable factors that confer susceptibility is essential for intervention. We evaluated whether Toll-like receptor 2 (TLR2) methylation, a reversible immune-epigenetic process, and its dietary modulation by flavonoids and methyl nutrients, modify susceptibility to heart rate variability effects following PM2.5 exposure. We measured heart rate variability and PM2.5 repeatedly over 11 years (1275 total observations) among 573 elderly men from the Normative Aging Study. Blood TLR2 methylation was analyzed using pyrosequencing. Daily flavonoid and methyl nutrients intakes were assessed through the Food Frequency Questionnaire (FFQ). Every 10 μg/m(3) increase in 48-hour PM2.5 moving average was associated with 7.74% (95% CI: -1.21% to 15.90%; P=0.09), 7.46% (95% CI: 0.99% to 13.50%; P=0.02), 14.18% (95% CI: 1.14% to 25.49%; P=0.03), and 12.94% (95% CI: -2.36% to 25.96%; P=0.09) reductions in root mean square of successive differences, standard deviation of normal-to-normal intervals, low-frequency power, and high-frequency power, respectively. Higher TLR2 methylation exacerbated the root mean square of successive differences, standard deviation of normal-to-normal intervals, low-frequency, and high-frequency reductions associated with heightened PM2.5 (Pinteraction=0.006, 0.03, 0.05, 0.04, respectively). Every interquartile-range increase in flavonoid intake was associated with 5.09% reduction in mean TLR2 methylation (95% CI: 0.12% to 10.06%; P=0.05) and counteracted the effects of PM2.5 on low frequency (Pinteraction=0.05). No significant effect of methyl nutrients on TLR2 methylation was observed. Higher TLR2 methylation may confer susceptibility to adverse cardiac autonomic effects of PM2.5 exposure in older individuals. Higher flavonoid intake may attenuate these effects, possibly by decreasing TLR2 methylation. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 01/2015; 4(1). DOI:10.1161/JAHA.114.001423 · 2.88 Impact Factor
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    ABSTRACT: Abstract Preterm birth is a leading cause of infant mortality and can lead to poor life-long health and adverse neurodevelopmental outcomes. The pathophysiologic mechanisms that precede preterm labor remain elusive, and the role that epigenetic phenomena play is largely unstudied. The objective of this study was to assess the association between microRNA (miRNA) expression levels in cervical cells obtained from swabs collected during pregnancy and the length of gestation. We analyzed cervical samples obtained between 16 and 19 weeks of gestation from 53 women in a prospective cohort from Mexico City, and followed them until delivery. Cervical miRNA was extracted and expression was quantified using the NanoString nCounter Analysis System. Linear regression models were used to examine the association between miRNA expression levels and gestational age at delivery, adjusted for maternal age, education, parity, body mass index, smoke exposure, and inflammation assessed on a Papanicolaou smear. We identified six miRNAs that were significantly associated with gestational age at the time of delivery, including miR-21, 30e, 142, 148b, 29b, and 223. Notably, per each doubling in miR-21 expression, gestations were 0.9 (95% CI: 0.2-1.5) days shorter on average (P = 0.009). Per each doubling in miR-30e, 142, 148b, 29b, and 223 expression, gestations were shorter by 1.0 to 1.6 days. The predicted targets of the miRNAs were enriched for molecules involved in DNA replication and inflammatory processes. The levels of specific miRNAs in the human cervix during pregnancy are predictive of gestational age at delivery, and should be validated in future studies as potential biomarkers of preterm birth risk.
    Epigenetics: official journal of the DNA Methylation Society 01/2015; DOI:10.1080/15592294.2015.1006498 · 5.11 Impact Factor
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    ABSTRACT: Objective. To examine the association of maternal glycemia during pregnancy and after delivery with anthropometry in the offspring of mothers with gestational diabetes mellitus (GDM). Methods. A total of 1,263 GDM mothers and their children finished the health survey at 1-5 years after delivery. Results. Offspring of GDM mothers who were diagnosed with diabetes during pregnancy had higher prevalence of overweight, higher mean weight for height Z scores, and higher mean BMI for age Z scores at 1-5 years old than the offspring of GDM mothers who were diagnosed with impaired glucose tolerance (IGT) during pregnancy. Offspring of GDM mothers who developed diabetes 1-5 years after delivery had higher mean values of Z scores for weight for height and BMI for age at 1-5 years old than the offspring of GDM mothers who had normal glucose or prediabetes after delivery. Conclusions. Offspring of GDM mothers who were diagnosed with diabetes during pregnancy or after delivery had an increased risk of childhood overweight or weight gain at 1-5 years old compared with children of GDM mothers with IGT during pregnancy or with normal glucose or prediabetes after delivery.
    01/2015; 2015:543038. DOI:10.1155/2015/543038
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    ABSTRACT: Cardiovascular disease risk has been consistently linked with particulate matter (PM) exposure. Cell-derived microvesicles (MVs) are released into plasma and transfer microRNAs (miRNAs) between tissues. MVs can be produced by the respiratory system in response to proinflammatory triggers, enter the circulatory system and remotely modify gene expression in cardiovascular tissues. However, whether PM affects MV signaling has never been investigated. In this study, we evaluated expression of microRNAs contained within plasma MVs upon PM exposure both in vivo and in vitro. In the in vivo study, we isolated plasma MVs from healthy steel plant workers before and after workplace PM exposure. We measured the expression of 88 MV-associated miRNAs by real-time polymerase chain reaction. To assess a possible source of the MV miRNAs identified in vivo, we measured their miRNA expression in PM-treated A549 pulmonary cell lines in vitro. MiRNA profiling of plasma MVs showed 5.62- and 13.95-fold increased expression of miR-128 and miR-302c, respectively, after 3 days of workplace PM exposure (P < 0.001). According to Ingenuity Pathway Analysis, miR-128 is part of coronary artery disease pathways, and miR-302c is part of coronary artery disease, cardiac hypertrophy and heart failure pathways. In vitro experiments confirmed a dose-dependent expression of miR-128 in MVs released from A549 cells after 6 h of PM treatment (P = 0.030). MiR-302c was expressed neither from A549 cells nor in reference lung RNA. These results suggest novel PM-activated molecular mechanisms that may mediate the effects of air pollution and could lead to the identification of new diagnostic and therapeutic interventions. Copyright © 2014 The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd.
    Journal of Applied Toxicology 01/2015; 35(1). DOI:10.1002/jat.2987 · 3.17 Impact Factor
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    ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are known endocrine disrupting chemicals used commonly as flame retardants in everything from electronics to furniture. Exposure to PBDEs during early development has been linked to neurodevelopmental delays. Despite mounting evidence of neurological harm from PBDE exposure, the molecular mechanisms underlying these effects on brain function remain unknown. We examined the effects of perinatal exposure to BDE-47, the most biologically active and prevalent BDE congener in North America, on epigenetic patterns in the frontal lobe of Wistar rats. Dams were gavaged with BDE-47 (0.002 and 0.2 mg/kg body weight) at gestation days 9 and 16, and postnatal days 1, 8, and 15. Frontal lobes from offspring at postnatal day 41 were collected to measure 5-methylcytosine (5mC) in mitochondrial cytochrome c oxidase genes (Mt-co1, Mt-co2, and Mt-co3), global nuclear 5-hydroxymethylcytosine (5hmC) content, 5mC in repetitive elements L1Rn, and 5mC in nuclear genes (Bdnf, Crhr1, Mc2r, Nr3c1, and Snca) related to behavioral and brain functions in the nuclear genome. We observed a significant decrease in %5mC in Mt-co2 (difference from control = −0.68%, p = 0.01 at the 0.2 mg/kg BDE-47). 5mC in repetitive elements L1Rn decreased at 0.002 mg/kg BDE-47 (difference = −1.23%, p = 0.02). Decreased nuclear 5mC was observed in Bdnf and Nr3c1 in BDE-47 exposed rats. However, we did not observe significant effects of PBDE toxicity on DNA methylation patterns for the majority of genes in the brain.
    Toxicology 12/2014; DOI:10.1016/j.tox.2014.12.019 · 3.75 Impact Factor

Publication Stats

7k Citations
1,354.68 Total Impact Points

Institutions

  • 2008–2015
    • Harvard University
      • Department of Environmental Health
      Cambridge, Massachusetts, United States
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
    • Ospedale Maggiore Carlo Alberto Pizzardi di Bologna
      Bolonia, Emilia-Romagna, Italy
  • 2007–2015
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 2000–2014
    • University of Milan
      • • Department of Occupational and Environmental Health
      • • Department of Medical Sciences
      Milano, Lombardy, Italy
  • 2013
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
    • Kresge Eye Institute
      Detroit, Michigan, United States
  • 2012
    • Columbia University
      • Department of Environmental Health Sciences
      New York City, NY, United States
    • Università degli Studi di Sassari
      Sassari, Sardinia, Italy
    • Uniformed Services University of the Health Sciences
      • Department of Preventive Medicine & Biometrics
      Bethesda, MD, United States
    • Brigham and Women's Hospital
      • Channing Division of Network Medicine
      Boston, MA, United States
    • Boston College, USA
      Boston, Massachusetts, United States
  • 2009–2012
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      • Occupational Medicine 1
      Milano, Lombardy, Italy
  • 2002–2008
    • National Institutes of Health
      • Branch of Genetic Epidemiology
      Maryland, United States
  • 2003–2006
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Genetic Epidemiology
      Bethesda, MD, United States
  • 2004
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • Northern Inyo Hospital
      BIH, California, United States
    • Università degli studi di Parma
      Parma, Emilia-Romagna, Italy
  • 2001–2004
    • NCI-Frederick
      Maryland, United States