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  • Llop, Sabrina, et al. (författare)
  • CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment
  • 2017
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 105, s. 34-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. Objectives We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. Methods The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n = 1160, 20 and 30 months of age, studied during the years 2001–2012), two subcohorts from Spain (INMA) (n = 625, 14 months of age, 2003–2009), and two subcohorts from Italy and Greece (PHIME) (n = 854, 18 months of age, 2006–2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). Results There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95% CI]: = 2.9[1.53,4.27] for CYP3A7 rs2257401 GG + GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA + AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG + AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p < 0.05) in European cohorts only. Conclusions Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.
  • Lozano, Manuel, et al. (författare)
  • DNA methylation changes associated with prenatal mercury exposure : A meta-analysis of prospective cohort studies from PACE consortium
  • 2022
  • Ingår i: Environmental Research. - : Elsevier. - 0013-9351. ; 204:Pt B, s. 112093-
  • Tidskriftsartikel (refereegranskat)abstract
    • Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10−5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10−7) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10−7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
  • Wang, Gang, et al. (författare)
  • Spirometric phenotypes from early childhood to young adulthood : a Chronic Airway Disease Early Stratification study
  • 2021
  • Ingår i: ERJ Open Research. - : ERS Publications. - 2312-0541. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.Methods: We studied 49334 participants from 14 population-based cohorts in different age groups (⩽10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ⩾LLN, and FVC z-score Results: The prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m−2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46).Conclusion: Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.
  • Analitis, Antonis, et al. (författare)
  • Synergistic Effects of Ambient Temperature and Air Pollution on Health in Europe : Results from the PHASE Project
  • 2018
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 15:9, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the potential synergy between air pollution and meteorology and their impact on mortality in nine European cities with data from 2004 to 2010. We used daily series of Apparent Temperature (AT), measurements of particulate matter (PM10), ozone (O₃), and nitrogen dioxide (NO₂) and total non-accidental, cardiovascular, and respiratory deaths. We applied Poisson regression for city-specific analysis and random effects meta-analysis to combine city-specific results, separately for the warm and cold seasons. In the warm season, the percentage increase in all deaths from natural causes per °C increase in AT tended to be greater during high ozone days, although this was only significant for all ages when all causes were considered. On low ozone days, the increase in the total daily number of deaths was 1.84% (95% CI 0.87, 2.82), whilst it was 2.20% (95% CI 1.28, 3.13) in the high ozone days per 1 °C increase in AT. Interaction with PM10 was significant for cardiovascular (CVD) causes of death for all ages (2.24% on low PM10 days (95% CI 1.01, 3.47) whilst it is 2.63% (95% CI 1.57, 3.71) on high PM10 days) and for ages 75+. In days with heat waves, no consistent pattern of interaction was observed. For the cold period, no evidence for synergy was found. In conclusion, some evidence of interactive effects between hot temperature and the levels of ozone and PM10 was found, but no consistent synergy could be identified during the cold season.
  • Bustamante, Mariona, et al. (författare)
  • A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways.
  • 2016
  • Ingår i: Human molecular genetics. - 1460-2083. ; 25:18, s. 4127-4142
  • Tidskriftsartikel (refereegranskat)abstract
    • More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistical tests were applied to the 1000 Genomes imputed genotypic data. The meta-analysis (N = 5758) followed by replication (N = 3784) identified a genome-wide significant association between rs8111874 and diarrhoea at age 1 year. Conditional analysis suggested that the causal variant could be rs601338 (W154X) in the FUT2 gene. Children with the A allele, which results in a truncated FUT2 protein, had lower risk of diarrhoea. FUT2 participates in the production of histo-blood group antigens and has previously been implicated in the susceptibility to infections, including Rotavirus and Norovirus Gene-set enrichment analysis suggested pathways related to the histo-blood group antigen production, and the regulation of ion transport and blood pressure. Among others, the gastrointestinal tract, and the immune and neuro-secretory systems were detected as relevant organs. In summary, this genome-wide association meta-analysis suggests the implication of the FUT2 gene in diarrhoeal disease in young children from the general population.
  • de' Donato, Francesca K., et al. (författare)
  • Changes in the effect of heat on mortality in the last 20 years in nine European cities : results from the PHASE project
  • 2015
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 12:12, s. 15567-15583
  • Tidskriftsartikel (refereegranskat)abstract
    • The European project PHASE aims to evaluate patterns of change in the temperature–mortality relationship and in the number of deaths attributable to heat in nine European cities in two periods, before and after summer 2003 (1996–2002 and 2004–2010). We performed age-specific Poisson regression models separately in the two periods, controlling for seasonality, air pollution and time trends. Distributed lag non-linear models were used to estimate the Relative Risks of daily mortality for increases in mean temperature from the 75th to 99th percentile of the summer distribution for each city. In the recent period, a reduction in the mortality risk associated to heat was observed only in Athens, Rome and Paris, especially among the elderly. Furthermore, in terms of heat-attributable mortality, 985, 787 and 623 fewer deaths were estimated, respectively, in the three cities. In Helsinki and Stockholm, there is a suggestion of increased heat effect. Noteworthy is that an effect of heat was still present in the recent years in all cities, ranging from +11% to +35%. In Europe, considering the warming observed in recent decades and population ageing, effective intervention measures should be promoted across countries, especially targeting vulnerable subgroups of the population with lower adaptive resources.
  • Michelozzi, Paola, et al. (författare)
  • High temperature and hospitalizations for cardiovascular and respiratory causes in 12 European cities.
  • 2009
  • Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 179:5, s. 383-9
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE: Episode analyses of heat waves have documented a comparatively higher impact on mortality than on morbidity (hospital admissions) in European cities. The evidence from daily time series studies is scarce and inconsistent. OBJECTIVES: To evaluate the impact of high environmental temperatures on hospital admissions during April to September in 12 European cities participating in the Assessment and Prevention of Acute Health Effects of Weather Conditions in Europe (PHEWE) project. METHODS: For each city, time series analysis was used to model the relationship between maximum apparent temperature (lag 0-3 days) and daily hospital admissions for cardiovascular, cerebrovascular, and respiratory causes by age (all ages, 65-74 age group, and 75+ age group), and the city-specific estimates were pooled for two geographical groupings of cities. MEASUREMENTS AND MAIN RESULTS: For respiratory admissions, there was a positive association that was heterogeneous between cities. For a 1 degrees C increase in maximum apparent temperature above a threshold, respiratory admissions increased by +4.5% (95% confidence interval, 1.9-7.3) and +3.1% (95% confidence interval, 0.8-5.5) in the 75+ age group in Mediterranean and North-Continental cities, respectively. In contrast, the association between temperature and cardiovascular and cerebrovascular admissions tended to be negative and did not reach statistical significance. CONCLUSIONS: High temperatures have a specific impact on respiratory admissions, particularly in the elderly population, but the underlying mechanisms are poorly understood. Why high temperature increases cardiovascular mortality but not cardiovascular admissions is also unclear. The impact of extreme heat events on respiratory admissions is expected to increase in European cities as a result of global warming and progressive population aging.
  • Perez, Laura, et al. (författare)
  • Chronic burden of near-roadway traffic pollution in 10 European cities (APHEKOM network)
  • 2013
  • Ingår i: European Respiratory Journal. - Sheffield, England : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 42:3, s. 594-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent epidemiological research suggests that near road traffic-related pollution may cause chronic disease, as well as exacerbate related pathologies, implying that the entire "chronic disease progression" should be attributed to air pollution, no matter what the proximate cause was. We estimated the burden of childhood asthma attributable to air pollution in 10 European cities by calculating the number of cases of 1) asthma caused by near road traffic-related pollution, and 2) acute asthma events related to urban air pollution levels. We then expanded our approach to include coronary heart diseases in adults.Derivation of attributable cases required combining concentration-response function (CRF) between exposures and the respective health outcome of interest (obtained from published literature), an estimate of the distribution of selected exposures in the target population, and information about the frequency of the assessed morbidities.Exposure to roads with high vehicle traffic, a proxy for near road traffic-related pollution, accounted for 14% of all asthma cases. When a causal relationship between near road traffic-related pollution and asthma is assumed, 15% of all episodes of asthma symptoms were attributable to air pollution. Without this assumption, only 2% of asthma symptoms were attributable to air pollution. Similar patterns were found for coronary heart diseases in older adults.Pollutants along busy roads are responsible for a large and preventable share of chronic disease and related acute exacerbation in European urban areas.
  • Scortichini, Matteo, et al. (författare)
  • The inter-annual variability of heat-related mortality in nine European cities (1990–2010)
  • 2018
  • Ingår i: Environmental health. - : BioMed Central. - 1476-069X .- 1476-069X. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The association between heat and daily mortality and its temporal variation are well known. However, few studies have analyzed the inter-annual variations in both the risk estimates and impacts of heat. The aim is to estimate inter-annual variations in the effect of heat for a fixed temperature range, on mortality in 9 European cities included in the PHASE (Public Health Adaptation Strategies to Extreme weather events) project for the period 1990-2010. The second aim is to evaluate overall summer effects and heat-attributable deaths for each year included in the study period, considering the entire air temperature range (both mild and extreme temperatures).METHODS: A city-specific daily time-series analysis was performed, using a generalized additive Poisson regression model, restricted to the warm season (April-September). To study the temporal variation for a fixed air temperature range, a Bayesian Change Point analysis was applied to the relative risks of mortality for a 2 °C increase over the 90th percentile of the city-specific distribution. The number of heat attributable deaths in each summer were also calculated for mild (reference to 95th percentile) and extreme heat (95th percentile to maximum value).RESULTS: A decline in the effects of heat over time was observed in Athens and Rome when considering a fixed interval, while an increase in effects was observed in Helsinki. The greatest impact of heat in terms of attributable deaths was observed in the Mediterranean cities (Athens, Barcelona and Rome) for extreme air temperatures. In the other cities the impact was mostly related to extreme years with 2003 as a record breaking year in Paris (+ 1900 deaths) and London (+ 1200 deaths).CONCLUSIONS: Monitoring the impact of heat over time is important to identify changes in population vulnerability and evaluate adaptation measures.
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