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1.
Epigenomics ; 11(13): 1487-1500, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31536415

RESUMO

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

2.
Sci Total Environ ; 656: 870-876, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30625673

RESUMO

Evidence is cumulating on the adverse health effects of environmental exposures on health of the fetus and the childbearing mothers. Among mother's conditions, gestational diabetes mellitus has been considered rarely in spite of its importance for both mother and child. We determined the role of maternal exposure to lead (Pb), cadmium (Cd) and manganese (Mn) to gestational diabetes mellitus (GDM) on diagnosed GDM and impaired glucose tolerance (IGT) in diabetes-free mothers from the French EDEN mother-child cohort. 623 pregnant women without pre-existing diabetes were included in the study. GDM and IGT were diagnosed by a gynecologist during consultations after blood analysis. Pb, Cd and Mn were measured in second-trimester blood samples. Associations between ln-transformed concentrations of metals and GDM and IGT respectively were examined using multiple logistic regression analysis adjusted for potential confounders. The prevalences of GDM and IGT were 7.1% and 10.1% respectively. After adjustment for confounders, Cd was statistically related to having had a diagnosis of GDM or IGT (Adjusted Odds-Ratio (AOR): 1.61, 1.05-2.48), and Pb to GDM at borderline significance (AOR: 1.65, 0.82-3.34). Our findings add to the growing evidence supporting the role of maternal exposure to heavy toxic metals that persist longtime in the environment as a risk factor for GDM.


Assuntos
Diabetes Gestacional/epidemiologia , Poluentes Ambientais/efeitos adversos , Intolerância à Glucose/epidemiologia , Exposição Materna/efeitos adversos , Metais Pesados/efeitos adversos , Adulto , Diabetes Gestacional/induzido quimicamente , Feminino , França/epidemiologia , Intolerância à Glucose/induzido quimicamente , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Gravidez , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
3.
J Allergy Clin Immunol ; 143(6): 2062-2074, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30579849

RESUMO

BACKGROUND: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. OBJECTIVE: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. METHODS: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. RESULTS: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. CONCLUSION: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.

4.
J Allergy Clin Immunol ; 143(2): 808-809, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30553549
5.
PLoS One ; 13(11): e0207290, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30485327

RESUMO

Allergic rhinitis (AR) is a chronic disease affecting a large amount of the population. To optimize treatment and disease management, it is crucial to detect patients suffering from severe forms. Several tools have been used to classify patients according to severity: standardized questionnaires, visual analogue scales (VAS) and cluster analysis. The aim of this study was to evaluate the best method to stratify patients suffering from seasonal AR and to propose cut-offs to identify severe forms of the disease. In a multicenter French study (PollinAir), patients suffering from seasonal AR were assessed by a physician that completed a 17 items questionnaire and answered a self-assessment VAS. Five methods were evaluated to stratify patients according to AR severity: k-means clustering, agglomerative hierarchical clustering, Allergic Rhinitis Physician Score (ARPhyS), total symptoms score (TSS-17), and VAS. Fisher linear, quadratic discriminant analysis, non-parametric kernel density estimation methods were used to evaluate miss-classification of the patients and cross-validation was used to assess the validity of each scale. 28,109 patients were categorized into "mild", "moderate", and "severe", through the 5 different methods. The best discrimination was offered by the ARPhyS scale. With the ARPhyS scale, cut-offs at a score of 8-9 for mild to moderate and of 11-12 for moderate to severe symptoms were found. Score reliability was also acceptable (Cronbach's α coefficient: 0.626) for the ARPhyS scale, and excellent for the TSS-17 (0.864). The ARPhyS scale seems the best method to target patients with severe seasonal AR. In the present study, we highlighted optimal discrimination cut-offs. This tool could be implemented in daily practice to identify severe patients that need a specialized intervention.

6.
Am J Epidemiol ; 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30351340

RESUMO

International collaborations among birth cohorts to better understand asthma and allergies have increased in the last years. However, differences in definitions and methods preclude direct pooling of original individual participant data. We harmonized data from 14 birth cohorts, with three to 20 follow-ups, from nine European countries, as part of the Mechanisms of the Development of Asthma and Allergies (MeDALL) project. The harmonization process followed six steps: organization of the harmonization panel; identification of variables relevant to MeDALL objectives (candidate variables); proposal of a definition for each candidate variable (reference definition); assessment of the compatibility of each cohort variable to its reference definition (inferential equivalence) and classifications of this inferential equivalence as complete, partial, or impossible; workshop to agree on the reference definitions and classifications of inferential equivalence; and data preparation and delivery through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definition was classified as complete, partial and impossible for 70%, 15% and 15% of the variables, respectively. A harmonized database was delivered. In birth cohorts of asthma and allergies, the harmonization of data for pooled analyses is feasible and may achieve high inferential comparability. The MeDALL harmonization approach can be used in other collaborative projects.

7.
Eur Respir J ; 52(3)2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30209194

RESUMO

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.

8.
Lancet Respir Med ; 6(5): 379-388, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29496485

RESUMO

BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. FINDINGS: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p<1·14 × 10-7) after meta-analysis. Consistently lower methylation levels were observed at all associated loci across childhood from age 4 to 16 years in participants with asthma, but not in cord blood at birth. All 14 CpG sites were significantly associated with asthma in the second replication study using whole-blood DNA, and were strongly associated with asthma in purified eosinophils. Whole-blood transcriptional signatures associated with these CpG sites indicated increased activation of eosinophils, effector and memory CD8 T cells and natural killer cells, and reduced number of naive T cells. Five of the 14 CpG sites were associated with asthma in respiratory epithelial cells, indicating cross-tissue epigenetic effects. INTERPRETATION: Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context. FUNDING: EU and the Seventh Framework Programme (the MeDALL project).


Assuntos
Asma/genética , Ilhas de CpG , Metilação de DNA , Eosinófilos/imunologia , Epigênese Genética , Asma/sangue , Criança , Pré-Escolar , DNA/sangue , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Linfócitos T Citotóxicos
9.
Environ Health Perspect ; 126(2): 027002, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29398652

RESUMO

BACKGROUND: Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema. OBJECTIVES: We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals. METHODS: Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children's ages of 1-5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother-son pairs with adjusted multiple logistic regression and Cox's survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment. RESULTS: At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0-24 mo of age) eczema (15.7%) and late-onset (24-60 mo of age) eczema (14.7%). Applying the Cox's model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di-n-butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio (HR)=1.67 [95% confidence interval (CI): 1.10, 2.54], p=0.01 and HR=1.87 (95% CI: 1.01, 3.48), p=0.04, respectively}. CONCLUSIONS: Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. https://doi.org/10.1289/EHP1829.

11.
Allergy Rhinol (Providence) ; 8(3): 132-138, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29070270

RESUMO

Backgroud: Evidence about the relationship between prenatal maternal depression and the development of childhood asthma and allergies in early life is scarce. We aimed to examine this relationship by using data set of EDEN mother-child cohort study. A total of 1139 children were followed-up until the age of 5 years. METHODS: Prenatal maternal depression was self-reported by using the Centre for Epidemiological Studies-Depression scale (CES-D) questionnaire and was classified into binary variable (maternal depression [CES-D score of ≥16] and no maternal depression [CES-D score of <16]). Asthma and allergies in the first 5 years were assessed by using the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC). Adjusted odds ratio (aOR) was estimated for the relationship between prenatal maternal depression and early life asthma and allergies by marginal models through the method of generalized estimating equation (GEE) when adjusting for the confounders. RESULTS: In our study population, 13.67 % of the mothers had clinical significant depression (the total scores for CES-D ≥16) during pregnancy. For children ages 5 years, the prevalence of wheezing, physician-diagnosed asthma, physician-diagnosed eczema and allergic rhinoconjunctivitis were 46.78, 20.99, 29.17, and 22.54%, respectively. Prenatal maternal depression was associated with ever allergic rhinoconjunctivitis (aOR 1.87 [95% confidence interval {CI}, 1.33-2.62]). No significant relationships were found between prenatal maternal depression and wheezing, physician-diagnosed asthma and physician-diagnosed eczema (aOR 1.12 [95% CI, 0.91-1.39], aOR 1.23 [95% CI, 0.81-1.85] and aOR 1.17 [95% CI, 0.86-1.61], respecitvely). CONCLUSION: Prenatal maternal depression was related to ever allergic rhinoconjunctivitis in the first 5 years of life in children of EDEN mother-child cohort study.

12.
Hum Mol Genet ; 26(20): 4067-4085, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-29016858

RESUMO

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.


Assuntos
Herança Materna/genética , Obesidade/complicações , Resultado da Gravidez/genética , Adulto , Índice de Massa Corporal , Estudos de Coortes , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Herança Materna/fisiologia , Mães , Gravidez/fisiologia , Resultado da Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo
13.
Int J Chron Obstruct Pulmon Dis ; 12: 1363-1374, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28503065

RESUMO

Although French farmers smoke less on average than individuals from the general population, they suffer more from COPD. Exposure to biological and chemical air pollutants in the farm may be the cause of these higher COPD rates. This study investigates the role of bio-contaminants, including the relationship of exposure to volatile organic compounds (VOCs) and fine particulate matter (of diameter of 2.5 µm [PM2.5]) objectively measured in the farm settings (dwellings and workplaces) to serum cytokines involved in COPD, in a sample of 72 farmers from 50 farms in the Auvergne region, France. Mean concentrations of VOCs were highest inside the home, while levels of PM2.5 were highest in workplaces (stables and granaries). After adjusting for confounders, high exposure to PM2.5 was significantly associated with a decreased level of serum cytokines (among others, IL13: ß: -0.94, CI: -1.5 to -0.2, P-value =0.004; IL8: ß: -0.82, CI: -1.4 to -0.2, P-value =0.005) and high exposure to VOCs according to a VOC global score with a decreased IL13 level (ß: -0.5, CI: -0.9 to -0.1, P-value =0.01). Moreover, respiratory symptoms and diseases, including COPD, were associated with a decreased level of serum cytokines significantly in the case of IL5. An alteration of immune response balance in terms of cytokine levels in relation to indoor chemical air pollution exposure may contribute to respiratory health impairment in farmers.


Assuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Citocinas/sangue , Fazendeiros , Habitação , Exposição por Inalação/efeitos adversos , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Compostos Orgânicos Voláteis/efeitos adversos , Local de Trabalho , Adulto , Doenças dos Trabalhadores Agrícolas/sangue , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças dos Trabalhadores Agrícolas/imunologia , Biomarcadores/sangue , Monitoramento Ambiental , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/imunologia , Fatores de Risco
14.
Am J Epidemiol ; 185(6): 465-473, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28399567

RESUMO

Evidence on the association between mode of delivery and asthma at school age is inconclusive. We assessed the associations between specific modes of delivery and asthma in children from 9 European birth cohorts that enrolled participants between 1996 and 2006. Cohort-specific crude and adjusted risk ratios for asthma at ages 5-9 years were calculated using Poisson regression models and pooled. A sensitivity analysis was carried out in children born at term to reduce confounding due to perinatal factors. The study included 67,613 participants. Cohort-specific rates of cesarean delivery varied from 9.4% to 37.5%. Cesarean delivery, as opposed to vaginal delivery, was associated with an increased risk of asthma (adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.02, 1.46). Compared with spontaneous vaginal delivery, the adjusted risk ratio was 1.33 (95% CI: 1.02, 1.75) for elective cesarean delivery, 1.07 (95% CI: 0.94, 1.22) for emergency cesarean delivery, and 0.97 (95% CI: 0.84, 1.12) for operative vaginal delivery. In children born at term, the associations were strengthened only for elective cesarean delivery (aRR = 1.49, 95% CI: 1.13, 1.97). The large sample size allowed analysis of the associations between specific modes of delivery and asthma at school age. The increased risk of asthma associated with elective cesarean delivery, especially among children born at term, is relevant in counteracting the increasing use of this procedure, which is often performed without a clear medical indication.


Assuntos
Asma/etiologia , Cesárea/efeitos adversos , Parto Obstétrico/métodos , Asma/epidemiologia , Cesárea/estatística & dados numéricos , Criança , Pré-Escolar , Estudos de Coortes , Parto Obstétrico/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Europa (Continente)/epidemiologia , Humanos , Distribuição de Poisson , Prevalência , Estudos Prospectivos , Nascimento a Termo
15.
Artigo em Inglês | MEDLINE | ID: mdl-28420222

RESUMO

The advent of the exposome concept, the advancement of mobile technology, sensors, and the "internet of things" bring exciting opportunities to exposure science. Smartphone apps, wireless devices, the downsizing of monitoring technologies, along with lower costs for such equipment makes it possible for various aspects of exposure to be measured more easily and frequently. We discuss possibilities and lay out several criteria for using smart technologies for external exposome studies. Smart technologies are evolving quickly, and while they provide great promise for advancing exposure science, many are still in developmental stages and their use in epidemiology and risk studies must be carefully considered. The most useable technologies for exposure studies at this time relate to gathering exposure-factor data, such as location and activities. Development of some environmental sensors (e.g., for some air pollutants, noise, UV) is moving towards making the use of these more reliable and accessible to research studies. The possibility of accessing such an unprecedented amount of personal data also comes with various limitations and challenges, which are discussed. The advantage of improving the collection of long term exposure factor data is that this can be combined with more "traditional" measurement data to model exposures to numerous environmental factors.


Assuntos
Exposição Ambiental/análise , Monitoramento Ambiental/instrumentação , Humanos , Modelos Teóricos
16.
Immun Inflamm Dis ; 5(1): 37-44, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28250923

RESUMO

INTRODUCTION: It has been suggested that human in utero exposure to heavy metals such as selenium can reduce the prevalence of childhood asthma and allergic diseases. However, data on this topic are scarce. The objective of the present study was to assess the putative associations between maternal selenium level during pregnancy and the risk of asthma, wheezing, allergic rhinitis, and atopic dermatitis in children from the EDEN birth cohort by the age of 1 and 3 years. METHODS: Plasma selenium concentrations were measured in maternal blood during mid-pregnancy (24-28 weeks of gestation) in 861 mothers. Cohort children were followed up from birth to 3 years using health questionnaires filled out by the parents for asthma, wheezing, allergic rhinitis, and atopic dermatitis. Maternal plasma selenium was related to the childhood outcomes by the age of 1 and 3 years. RESULTS: Our results showed a significant negative association between a high maternal plasma selenium level during pregnancy and the risk of wheezing in the child by the age of 1 and 3 years. However, maternal plasma selenium during pregnancy was not associated with the prevalence of asthma, allergic rhinitis or atopic dermatitis. CONCLUSIONS: The results of this study suggest that the level of fetal exposure to maternal selenium could have an influence on the risk of wheezing in infancy and potentially on the risk of developing asthma later in life.


Assuntos
Sons Respiratórios , Selênio/sangue , Adulto , Asma/epidemiologia , Pré-Escolar , Dermatite Atópica/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Troca Materno-Fetal , Gravidez , Rinite Alérgica/epidemiologia , Risco , Adulto Jovem
17.
Pediatr Allergy Immunol ; 28(3): 273-279, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28140475

RESUMO

BACKGROUND: It is known that asthma is related to obesity but also to small birthweight. The objective of this study was to clarify this issue by assessing the putative relationship between the changes in corpulence between birth and childhood as assessed by body mass index (BMI) and asthma phenotypes. METHODS: The following status in corpulence was assessed in 7781 schoolchildren using quartile of BMI at birth and at around 10 (9-11 years): underweight at birth and at around 10, underweight at birth and overweight at around 10, overweight at birth and underweight at around 10, overweight at birth and at around 10, and the reference group constituted by all the other children in whom corpulence changes were not extreme. Determination of asthma phenotypes (allergic, non-allergic, and exercise-induced asthma) was based on a clinical examination including skin prick tests, an exercise challenge test, and a questionnaire. RESULTS: The risk of allergic asthma was higher in children with persistent underweight, children with persistent overweight, and children becoming markedly more corpulent. In boys, the risk of allergic asthma was significantly higher for the less corpulent children at birth, regardless of whether they remained so or become overweight. In girls, the risk of allergic asthma was significantly higher in those with persistent overweight. There were no significant associations between BMI changes and non-allergic and exercise-induced asthma. CONCLUSIONS: We observed that some extreme changes in BMI, persistent underweight, and persistent overweight in childhood increased the risk of allergic asthma.


Assuntos
Asma/etiologia , Índice de Massa Corporal , Sobrepeso/complicações , Magreza/complicações , Asma/epidemiologia , Peso ao Nascer , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Fenótipo , Fatores de Risco , Testes Cutâneos , Inquéritos e Questionários
18.
BMC Genomics ; 18(1): 25, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056824

RESUMO

BACKGROUND: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood. RESULTS: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of p < 1.14 × 10-7. Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease. CONCLUSION: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.


Assuntos
Desenvolvimento Infantil , Metilação de DNA , Epigênese Genética , Epigenômica , Criança , Pré-Escolar , Ilhas de CpG , Epigenômica/métodos , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Locos de Características Quantitativas , Fumar/efeitos adversos
20.
Am J Hum Genet ; 98(4): 680-96, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27040690

RESUMO

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.


Assuntos
Metilação de DNA , Epigênese Genética , Fumar/efeitos adversos , Asma/etiologia , Asma/genética , Criança , Pré-Escolar , Mapeamento Cromossômico , Fenda Labial/etiologia , Fenda Labial/genética , Fissura Palatina/etiologia , Fissura Palatina/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudos de Associação Genética , Humanos , Lactente , Recém-Nascido , Gravidez
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