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1.
QJM ; 117(4): 257-268, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37930885

RESUMO

BACKGROUND: Early-life exposure increases health risks throughout an individual's lifetime. Biological aging is influenced by early-life risks as a key process of disease development, but whether early-life risks could accelerate biological aging and elevate late-life mortality and morbidity risks remains unknown. Knowledge is also limited on the potential moderating role of healthy lifestyle. METHODS: We investigate associations of three early-life risks around birth, breastfeeding, maternal smoking and birth weight, with biological aging of 202 580 UK Biobank participants (54.9 ± 8.1 years old). Biological aging was quantified as KDM-BA, PhenoAge and frailty. Moderate alcohol intake, no current smoking, healthy diet, BMI <30 kg/m2 and regular physical activity were considered as healthy lifestyles. Mortality and morbidity data were retrieved from health records. RESULTS: Individual early-life risk factors were robustly associated with accelerated biological aging. A one-unit increase in the 'early-life risk score' integrating the three factors was associated with 0.060 (SE=0.0019) and 0.036-unit (SE = 0.0027) increase in z-scored KDM-BA acceleration and PhenoAge acceleration, respectively, and with 22.3% higher odds (95% CI: 1.185-1.262) of frailty. Increased chronological age and healthy lifestyles could mitigate the accelerations of KDM-BA and PhenoAge, respectively. Associations of early-life risk score with late-life mortality and morbidity were mediated by biological aging (proportions: 5.66-43.12%). KDM-BA and PhenoAge accelerations could significantly mediate the impact on most outcomes except anxiety, and frailty could not mediate the impact on T2D. CONCLUSION: Biological aging could capture and mediate the late-life health risks stemming from the early-life risks, and could be potentially targeted for healthy longevity promotion.


Assuntos
Fragilidade , Humanos , Pessoa de Meia-Idade , Fragilidade/epidemiologia , Envelhecimento , Fatores de Risco , Comportamentos Relacionados com a Saúde , Morbidade
3.
J Assist Reprod Genet ; 40(3): 527-536, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36609942

RESUMO

PURPOSE: To compare the expression profile of extracellular vesicle microRNAs (EV-miRNAs) derived from follicular fluid after a trigger with recombinant human chorionic gonadotropin (r-hCG) or with a gonadotropin-releasing hormone GnRH agonist (GnRH-a) for final oocyte maturation. METHODS: A retrospective analysis of a prospective cohort. Women undergoing in vitro fertilization at a tertiary university-affiliated hospital were recruited between 2014 and 2016. EV-miRNAs were extracted from the follicular fluid of a single follicle, and their expression was assessed using TaqMan Open Array®. Genes regulated by EV-miRNAs were analyzed using miRWalk2.0 Targetscan database, DAVID Bioinformatics Resources, Kyoto-Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO). RESULTS: Eighty-two women were included in the r-hCG trigger group and 9 in the GnRH-a group. Of 754 EV-miRNAs screened, 135 were detected in at least 50% of the samples and expressed in both groups and were further analyzed. After adjusting for multiple testing, 41 EV-miRNAs whose expression levels significantly differed between the two trigger groups were identified. Bioinformatics analysis of the genes regulated by these EV-miRNAs showed distinct pathways between the two triggers, including TGF-beta signaling, cell cycle, and Wnt signaling pathways. Most of these pathways regulate cascades associated with apoptosis, embryo development, implantation, decidualization, and placental development. CONCLUSIONS: Trigger with GnRH-a or r-hCG leads to distinct EV-miRNAs expression profiles and to downstream biological effects in ovarian follicles. These findings may provide an insight for the increased apoptosis and the lower implantation rates following GnRH-a trigger vs. r-hCG in cases lacking intensive luteal phase support.


Assuntos
Vesículas Extracelulares , MicroRNAs , Humanos , Feminino , Gravidez , MicroRNAs/genética , Líquido Folicular , Estudos Retrospectivos , Estudos Prospectivos , Indução da Ovulação , Placenta , Hormônio Liberador de Gonadotropina/genética , Fertilização in vitro , Gonadotropina Coriônica , Vesículas Extracelulares/genética
4.
J Hum Hypertens ; 31(11): 725-730, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28660887

RESUMO

Previous studies in general people indicated that hypertensive disorders of pregnancy (HDP) increased the risk of subsequent hypertension after delivery. Some studies found that women with gestational diabetes mellitus (GDM) had an increased risk of HDP. However, very few studies have assessed the association between HDP and the risk of postpartum hypertension among GDM women. To evaluate the association between HDP and the risk of postpartum hypertension among GDM women, a retrospective cohort study was conducted in 1261 women with prior GDM at their postpartum 1-5 years using the baseline data from Tianjin Gestational Diabetes Mellitus Prevention Program. Cox regression models were applied to assess the single and joint associations of having a history of HDP, maternal pre-pregnancy Body mass index (BMI) (normal weight, overweight and obesity), and weight change from preconception to post-delivery with the risk of subsequent hypertension among the GDM women. We found that GDM women with a history of HDP, high pre-pregnancy BMI and weight gain >7 kg from preconception to post-delivery had an increased risk of postpartum hypertension. Joint effects analysis revealed that the positive association between a history of HDP in the index pregnancy and the risk of postpartum hypertension was consistent in GDM women with different levels of pre-pregnancy BMI or weight gain from preconception to post-delivery. In conclusion, a history of HDP, high pre-pregnancy BMI and weight gain >7 kg from preconception to post-delivery increase the risk of subsequent hypertension in postpartum 1-5 years among GDM women.


Assuntos
Pressão Sanguínea , Diabetes Gestacional/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão/epidemiologia , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Distribuição de Qui-Quadrado , China/epidemiologia , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/fisiopatologia , Análise Multivariada , Obesidade/diagnóstico , Obesidade/epidemiologia , Gravidez , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Aumento de Peso
5.
J Hum Hypertens ; 31(11): 731-736, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28300070

RESUMO

Hypertensive disorders of pregnancy (HDP) as a group of medical complications in pregnancy are believed to be associated with an increased risk of poor fetal growth, but the influence on offspring's body composition is not clear. The aim of the present study was to evaluate the association between maternal HDP and overweight status in the offspring of mothers with gestational diabetes mellitus (GDM). A cross-sectional study among 1263 GDM mother-child pairs was performed in Tianjin, China. General linear models and logistic regression models were used to assess the associations of maternal hypertension in pregnancy with anthropometry and overweight status in the offspring from birth to 1-5 years old. Offspring of GDM mothers who were diagnosed with hypertensive disorders during pregnancy had higher mean values of Z-scores for birth weight for gestational age and birth weight for length, and higher mean values of Z-scores for weight for age, weight for length/height, and body mass index for age at 1-5 years old than those of GDM mothers with normal blood pressure during pregnancy. Maternal HDP were associated with increased risks of large for gestational age (OR 1.74, 95% CI 1.08-2.79) and macrosomia (OR 2.02, 95% CI 1.23-3.31) at birth and childhood overweight/obesity at 1-5 years old age (OR 1.88, 95% CI 1.16-3.04). For offspring of mothers with GDM, maternal hypertension during pregnancy was a risk factor for macrosomia at birth and childhood overweight and obesity, and controlling the maternal hypertension may be more important for preventing large-for-gestational-age babies and childhood obesity.


Assuntos
Pressão Sanguínea , Diabetes Gestacional/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologia , Obesidade Infantil/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Adiposidade , Adulto , Fatores Etários , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Distribuição de Qui-Quadrado , China/epidemiologia , Estudos Transversais , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Feminino , Idade Gestacional , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/fisiopatologia , Modelos Lineares , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Obesidade Infantil/diagnóstico , Obesidade Infantil/fisiopatologia , Gravidez , Fatores de Risco , Fatores de Tempo , Aumento de Peso
6.
Biol Trace Elem Res ; 174(1): 71-81, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27129315

RESUMO

Previous studies revealed associations of urinary Cd (U-Cd), a chronic Cd exposure biomarker, with blood pressure (BP) in non-pregnant adults. However, the evidence regarding trimester-specific blood pressure in pregnancy and U-Cd and effect modification by dietary intake of micronutrients is scarce. We randomly selected 653 women from the Omega Study cohort. U-Cd was quantified by inductively coupled plasma mass spectrometry. Trimester-specific, systolic (SBP) and diastolic blood pressure (DBP) were determined employing standard protocols and mean arterial pressure (MAP) was also calculated. Associations of SBP, DBP, and MAP with U-Cd tertiles (≤0.21; 0.22-0.41; ≥0.42 µg/g Cr) were assessed using multivariable linear regression models. We also explored effect modification by pre-pregnancy BMI (≤25 or >25 kg/m2) or low/high micronutrients intake. After adjusting confounders in women with elevated (upper tertile) as compared with those with low (lowest tertile) U-Cd (≥0.42 vs. ≤0.21 µg/g Cr, respectively) had reduced third trimester MAP (-1.8; 95 % confidence interval (CI) = -3.1, -0.5 mmHg) and second trimester MAP (-1.1; 95 % CI = -2.3, -0.03 mmHg). A significant decrease in third-trimester MAP associated with increased U-Cd was observed only among normal/underweight women (BMI ≤ 25 kg/m2) and women with high dietary intake of micronutrients (calcium, magnesium, zinc, and selenium). Notably, U-Cd concentrations increased with the increased consumption of zinc and non-heme iron food sources. No significant differences in U-Cd concentrations were found in preeclamptic women compared with non-preeclamptic women. Our study provides evidence that dietary intake of micronutrients should be taken into account when assessing the health effects of Cd in pregnant women.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Cádmio/urina , Micronutrientes/administração & dosagem , Trimestres da Gravidez/urina , Gravidez/urina , Adulto , Feminino , Humanos
7.
J Thromb Haemost ; 13(5): 768-74, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25678264

RESUMO

BACKGROUND: Literature relating air pollution exposure to deep vein thrombosis (DVT) and pulmonary embolism (PE), despite 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. 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 United States. METHODS: We estimated daily exposure of PM2.5 in each ZIP code. We investigated the 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 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. RESULTS: A 10-µg m(-3) increase in short-term exposure was associated with a 0.63% increase in DVT admissions (95% confidence interval [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 Environmental Protection Agency annual standard of 12 µg m(-3) . CONCLUSIONS: 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.


Assuntos
Material Particulado/toxicidade , Admissão do Paciente , Trombose Venosa/etiologia , Idoso , Exposição Ambiental , Feminino , Humanos , Masculino , New England/epidemiologia , Trombose Venosa/epidemiologia
8.
Placenta ; 35(9): 665-72, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25047690

RESUMO

BACKGROUND: Epigenetics is tissue-specific and potentially even cell-specific, but little information is available from human reproductive studies about the concordance of DNA methylation patterns in cord blood and placenta, as well as within-placenta variations. We evaluated methylation levels at promoter regions of candidate genes in biological ageing pathways (SIRT1, TP53, PPARG, PPARGC1A, and TFAM), a subtelomeric region (D4Z4) and the mitochondrial genome (MT-RNR1, D-loop). METHODS: Ninety individuals were randomly chosen from the ENVIRONAGE birth cohort to evaluate methylation concordance between cord blood and placenta using highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen individuals, a more extensive sampling scheme was performed to examine within-placenta variation. RESULTS: The DNA methylation levels of the subtelomeric region and mitochondrial genome showed concordance between cord blood and placenta with correlation coefficients ranging from r = 0.31 to 0.43, p ≤ 0.005, and also between the maternal and foetal sides of placental tissue (r = 0.53 to 0.72, p ≤ 0.05). For the majority of targets, an agreement in methylation levels between four foetal biopsies was found (with intra-class correlation coefficients ranging from 0.16 to 0.72), indicating small within-placenta variation. CONCLUSIONS: The methylation levels of the subtelomeric region (D4Z4) and mitochondrial genome (MT-RNR1, D-loop) showed concordance between cord blood and placenta, suggesting a common epigenetic signature of these targets between tissues. Concordance was lacking between the other genes that were studied. In placental tissue, methylation patterns of most targets on the mitochondrial-telomere axis were not strongly influenced by sample location.


Assuntos
Envelhecimento/metabolismo , Metilação de DNA , Sangue Fetal/química , Genoma Mitocondrial , Placenta/metabolismo , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Gravidez , Regiões Promotoras Genéticas , Telômero/metabolismo , Adulto Jovem
9.
Environ Res ; 132: 76-82, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24742731

RESUMO

BACKGROUND: Epidemiological studies have shown associations of particulate matter (PM) exposure with hypercoagulability and thrombosis. Extracellular circulating histones have recently been identified as novel mediators of inflammatory and procoagulant responses. The potential roles of extracellular histones in PM-related hypercoagulability have yet not been investigated. OBJECTIVES: In 63 steel workers, we evaluated the effects of exposure to PM and PM metal components on two extracellular histone modifications (H3K4me3 and H3K9ac); and the association of H3K4me3 and H3K9ac with coagulation markers. METHODS: Extracellular H3K4me3 and H3K9ac were determined in plasma through enzyme-linked immunosorbent assays. Coagulation markers included endogenous thrombin potentials (ETPs), tissue-type plasminogen activator antigen (t-PA) and D-dimer. Exposure to PM with aerodynamic diameters <1 µm (PM1) or <10 µm (PM10) and PM10 metal components were estimated for each participant. RESULTS: The coagulation marker ETP, measured in the presence of soluble thrombomodulin (ETP TM+), showed significant positive associations with PM1 (ß=107.84, p=0.03), PM10 (ß=83.06, p=0.02), and zinc (ß=75.14, p=0.03); and a marginal association with iron (ß=122.58, p=0.07). Additional PM effects were observed on t-PA, D-dimer, and ETP TM+. PM1 exposure was associated with increased plasma H3K4me3 and H3K9ac (ß=0.20, p=0.02; ß=0.16, p=0.05, respectively). H3K4me3, but not H3K9ac, was associated with zinc (ß=0.13, p=0.03) and iron (ß=0.32, p=0.01) contained in PM. ETP TM+ was increased in association with higher plasma H3K4me3 (ß=0.50, p=0.05) and H3K9ac (ß=0.54, p=0.05). CONCLUSIONS: This observational study suggests potential roles of extracellular histones in PM-induced hypercoagulability. Experimental studies are warranted to further characterize these findings.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Histonas/metabolismo , Metais/toxicidade , Material Particulado/toxicidade , Adulto , Indústrias Extrativas e de Processamento , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos
10.
Clin Exp Allergy ; 44(5): 681-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24131275

RESUMO

BACKGROUND: Genetic variation in the ß-2 adrenergic receptor gene (ADRB2) has been implicated in asthma severity and control with conflicting results. Epigenetic variation in the ADRB2 may play an important role in asthma phenotype. OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage DNA methylation across the sites was evaluated for association with asthma severity (report of dyspnoea, night-time symptoms, rescue medication use, and baseline spirometry) and morbidity (school absences and unscheduled healthcare visits). Three clades composed of highly correlated methylation sites within the methylated segment of ADRB2 were further analysed. RESULTS: Methylation of individual sites generally ranged from 0% to 6% with average percentage methylation across sites of 2.4%. Univariate analyses strongly favoured the association of higher percentage methylation with lower asthma severity measured by report of dyspnoea. Furthermore, there was a non-significant trend towards less rescue medication use, night-time symptoms, school absences, activity limitation due to asthma, and improved lung function measurements with increased methylation. Multivariate analysis demonstrated methylation of ADRB2 gene significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites showed a strong, but not statistically significant, effect on decreased dyspnoea. CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is associated with decreased asthma symptom severity, suggesting a role for methylation in asthma phenotypes.


Assuntos
Asma/genética , Asma/fisiopatologia , Metilação de DNA , Receptores Adrenérgicos beta 2/genética , Asma/diagnóstico , Criança , Cidades , Ilhas de CpG , Dispneia/genética , Dispneia/fisiopatologia , Epigênese Genética , Feminino , Humanos , Masculino , Fenótipo , Regiões Promotoras Genéticas , Locos de Características Quantitativas , Testes de Função Respiratória , Rinite , Fatores de Risco , Índice de Gravidade de Doença
11.
Med Lav ; 103(2): 84-95, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22619984

RESUMO

INTRODUCTION: Global genomic hypomethylation is a common event in cancer tissues that is frequently observed in hematopoietic malignancies, including leukemia. Benzene, an established leukemogen at high doses, has been suggested to induce hypomethylation based on investigations of DNA methylation in LINE-1 and Alu repetitive elements. Whether global genomic DNA methylation content is reduced in response to benzene exposure is still undetermined. METHODS: We measured global DNA methylation in 78 gasoline station attendants and 58 controls in peripheral blood cells using high-resolution gas chromatography-mass spectrometry. PCR-Pyrosequencing measures of DNA methylation at Alu and LINE-1 repetitive elements, representing a large proportion of methylation in non-coding regions, were also available. Exposure markers included personal airborne benzene, and urinary benzene, t,t-muconic acid (t,t-MA) and S-phelylmercapturic acid. RESULTS: Mean global DNA methylation was 5.474 (+/- 0.083) %5mC in controls and 5.409 (+/- 0.142) %5mC in exposed participants (p = 0.01). All methylation markers were negatively correlated with airborne benzene. Alu and LINE-1 methylation, but not global DNA methylation, were negatively associated with t,t-MA; no association with the other urinary biomarkers was found. Multiple linear regression analysis adjusted for gender and age confirmed the results of correlation analysis and showed a 1.6% decrease in global DNA methylation associated with being gasoline station attendants. Alu and LINE-1 methylation levels were not associated with global DNA methylation. CONCLUSION: Our results show that benzene exposure is associated with alterations in both global DNA and repetitive element methylation. Global and repetitive element methylation levels are not correlated in blood DNA, likely representing independent responses to benzene exposure.


Assuntos
Benzeno/efeitos adversos , Metilação de DNA , Exposição por Inalação/efeitos adversos , Exposição Ocupacional/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/análise , Benzeno/análise , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Genômica , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/urina , Humanos , Exposição por Inalação/análise , Masculino , Computação Matemática , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Reação em Cadeia da Polimerase , Análise de Regressão , Sequências Repetitivas de Ácido Nucleico
12.
G Ital Med Lav Ergon ; 34(3 Suppl): 648-50, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23405741

RESUMO

Blood hypo-methylation mediates the effects of metal-rich airborne particles on blood coagulation: An occupational epidemiological study. Particulate matter (PM) exposure is associated with increased coagulation and thrombosis, but the biological mechanism has not yet been clarified. DNA methylation represents a potential mechanism because it can be modified by environmental factors. Foundry workers are exposed to PM components and showed increased cardiovascular risk. In a group of 63 steel workers we found that PM and zinc airborne levels were negatively associated with leukocyte DNA methylation in genes NOS3 and ET-1 (b = -1.1; p = 0.002 and b = -1.5; p = 0.003, for zinc exposure respectively in multivariate regression models; b = -0.9 with p = 0.01 for PM10 exposure and NOS3) and in turn, DNA hypo-methylation resulted associated with increased Endogenous Thrombin Potential (for NOS3 b = -45.0, p = 0.001; and for ET-1 b = -16.4, p = 0.03). Our study based on healthy subject exposed in occupational setting, suggests that gene specific hypomethylation contributes to environmentally-induced hypercoagulability.


Assuntos
Coagulação Sanguínea/genética , Poeira , Epigênese Genética , Doenças Profissionais/epidemiologia , Doenças Profissionais/genética , Humanos , Masculino , Metais , Material Particulado
13.
Br J Cancer ; 106(3): 585-91, 2012 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-22173668

RESUMO

BACKGROUND: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer. METHODS: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case-control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n=192) and matched controls (n=384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. RESULTS: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43-4.13), 1.47(0.85-2.57), and 2.22 (1.28-3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. CONCLUSION: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.


Assuntos
Elementos Alu , Leucócitos/metabolismo , Elementos Nucleotídeos Longos e Dispersos , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Elementos Alu/genética , Estudos de Casos e Controles , China/epidemiologia , Metilação de DNA , DNA de Neoplasias/análise , DNA de Neoplasias/metabolismo , Feminino , Promoção da Saúde , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Neoplasias Gástricas/sangue , Saúde da Mulher
14.
Br J Cancer ; 105(11): 1772-5, 2011 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-22033273

RESUMO

BACKGROUND: There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case-control studies suggested an association between short blood telomere length (TL) and increased RCC risk. METHODS: We conducted a large population-based case-control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models. RESULTS: Median TL was 0.85 for both cases and controls (P=0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (P<0.001 and P=0.07, respectively), and African Americans had longer TL than Caucasians (P<0.001). CONCLUSION: These data do not support the hypothesis that blood TL is associated with RCC. This population-based case-control study is, to our knowledge, the largest investigation to date of TL and RCC.


Assuntos
Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/genética , Neoplasias Renais/sangue , Neoplasias Renais/genética , Telômero/genética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/genética , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Estados Unidos , Adulto Jovem
15.
Brain Behav Immun ; 25(6): 1078-83, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21296655

RESUMO

Epigenetics is believed to play a role in Alzheimer's disease (AD). DNA methylation, the most investigated epigenetic hallmark, is a reversible mechanism that modifies genome function and chromosomal stability through the addition of methyl groups to cytosine located in CpG dinucleotides to form 5 methylcytosine (5mC). Methylation status of repetitive elements (i.e. Alu, LINE-1 and SAT-α) is a major contributor of global DNA methylation patterns and has been investigated in relation to a variety of human diseases. However, the role of methylation of repetitive elements in blood of AD patients has never been investigated so far. In the present study, a quantitative bisulfite-PCR pyrosequencing method was used to evaluate methylation of Alu, LINE-1 and SAT-α sequences in 43 AD patients and 38 healthy donors. In multivariate analysis adjusting for age and gender, LINE-1 was increased in AD patients compared with healthy volunteers (ADs: 83.6%5mC, volunteers: 83.1%5mC, p-value: 0.05). The group with best performances in mini mental state examination (MMSE) showed higher levels of LINE-1 methylation compared to the group with worst performances (MMSE>22: 83.9%5mC; MMSE≤22: 83.2%5mC; p=0.05). Our data suggest that LINE-1 methylation may lead to a better understanding of AD pathogenesis and course, and may contribute to identify novel markers useful to assess risk stratification. Further prospective investigations are warranted to evaluate the dynamics of DNA methylation from early-stage AD to advanced phases of the disease.


Assuntos
Elementos Alu/genética , Doença de Alzheimer/genética , Metilação de DNA , DNA Satélite/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteínas E/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Processamento de Proteína Pós-Traducional , Testes Psicológicos , Proteínas tau/líquido cefalorraquidiano
16.
Med Lav ; 101(6): 453-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21141348

RESUMO

BACKGROUND: Mexico is the third most populous country in America. A sizeable percentage of Mexicans live under unfavorable conditions such as malnutrition, marginalization and overcrowding. Environmental injustice includes: indigenous exposed to wood smoke, families living in mining zones, children working and living in garbage dumps and brick factories. Polycyclic aromatic hydrocarbons, pesticides, electronic waste and heavy metals exposure represent a health risk. These pollutants can induce biochemical lesions as DNA damage and epigenetic changes which could modif the gene expression profile of each individual. OBJECTIVES: The aim of this work is to create an Italy-Mexico collaboration (within the context of WHO collaborating centres) between the Center of Molecular and Genetic Epidemiology, University of Milan and the University of San Luis Potosi, will allow molecular approaches to develop early indicators of susceptibility to adult disease and cancer.


Assuntos
Centros Médicos Acadêmicos/organização & administração , Biomarcadores/análise , Proteção da Criança , Saúde Ambiental/organização & administração , Indicadores Básicos de Saúde , Cooperação Internacional , Populações Vulneráveis , Organização Mundial da Saúde/organização & administração , Acetilação , Criança , Pré-Escolar , Metilação de DNA , Poluentes Ambientais/efeitos adversos , Predisposição Genética para Doença , Histonas/química , Humanos , Lactente , Metilação , México , MicroRNAs/análise , MicroRNAs/genética , Processamento de Proteína Pós-Traducional
17.
Heredity (Edinb) ; 105(1): 105-12, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20179736

RESUMO

Epigenetics investigates heritable changes in gene expression that occur without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation and histone modifications, can change genome function under exogenous influence. We review current evidence indicating that epigenetic alterations mediate effects caused by exposure to environmental toxicants. Results obtained from animal models indicate that in utero or early-life environmental exposures produce effects that can be inherited transgenerationally and are accompanied by epigenetic alterations. The search for human equivalents of the epigenetic mechanisms identified in animal models is under way. Recent investigations have identified a number of environmental toxicants that cause altered methylation of human repetitive elements or genes. Some exposures can alter epigenetic states and the same and/or similar epigenetic alterations can be found in patients with the disease of concern. On the basis of current evidence, we propose possible models for the interplay between environmental exposures and the human epigenome. Several investigations have examined the relationship between exposure to environmental chemicals and epigenetics, and have identified toxicants that modify epigenetic states. Whether environmental exposures have transgenerational epigenetic effects in humans remains to be elucidated. In spite of the current limitations, available evidence supports the concept that epigenetics holds substantial potential for furthering our understanding of the molecular mechanisms of environmental toxicants, as well as for predicting health-related risks due to conditions of environmental exposure and individual susceptibility.


Assuntos
Exposição Ambiental , Epigênese Genética , Animais , Metilação de DNA/efeitos dos fármacos , Modelos Animais de Doenças , Suscetibilidade a Doenças , Poluentes Ambientais/toxicidade , Epigênese Genética/efeitos dos fármacos , Humanos
18.
J Epidemiol Community Health ; 64(1): 49-56, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19602472

RESUMO

BACKGROUND: Many studies have shown that exposures to air pollution are associated with cardiovascular events, although the mechanism remains to be clarified. To identify whether exposures to ambient particles act on autonomic function via the lipid/endothelial metabolism pathway, whether effects of particulate matter <2.5 mum in aerodynamic diameter (PM(2.5)) on heart rate variability (HRV) were modified by gene polymorphisms related to those pathways were evaluated. METHODS: HRV and gene data from the Normative Aging Study and PM(2.5) from a monitor located a kilometre from the examination site were used. A mixed model was fitted to investigate the associations between PM(2.5) and repeated measurements of HRV by gene polymorphisms of apolipoprotein E (APOE), lipoprotein lipase (LPL) and vascular endothelial growth factor (VEGF) adjusting for potential confounders chosen a priori. RESULTS: A 10 microg/m(3) increase in PM(2.5) in the 2 days before the examination was associated with 3.8% (95% CI 0.2% to 7.4%), 7.8% (95 CI 0.4% to 15.3%) and 10.6% (95% CI 1.8% to 19.4%) decreases of the standard deviation of normal-to-normal intervals, the low frequency and the high frequency, respectively. Overall, carriers of wild-type APOE, LPL and VEGF genes had stronger effects of particles on HRV than those with hetero- or homozygous types. Variations of LPL-N291S, LPL-D9N and APOE-G113C significantly modified effects of PM(2.5) on HRV. CONCLUSION: Associations between PM(2.5) and HRV were modified by gene polymorphisms of APOE, LPL and VEGF; the biological metabolism remains to be identified.


Assuntos
Poluentes Atmosféricos/farmacologia , Apolipoproteínas E/genética , Frequência Cardíaca/genética , Lipase Lipoproteica/genética , Material Particulado/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Endotélio/metabolismo , Genótipo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , Polimorfismo Genético
19.
J Thromb Haemost ; 8(4): 662-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19922434

RESUMO

BACKGROUND: Particulate matter (PM) exposure has been linked to increased risk of cardiovascular disease, possibly resulting from hypercoagulability and thrombosis. Lung and systemic inflammation resulting from PM inhalation may activate blood coagulation, but mechanisms for PM-related hypercoagulability are still largely unknown. OBJECTIVES: To identify coagulation mechanisms activated by PM in a population with well-characterized exposure. METHODS: We measured prothrombin time (PT), activated partial thromboplastin time, endogenous thrombin potentials (ETPs) with/without exogenous triggers and with/without soluble thrombomodulin, tissue-type plasminogen activator (t-PA) antigen, D-dimer and C-reactive protein (CRP) in 37 workers in a steel production plant with well-characterized exposure to PM with aerodynamic diameter of < 1 mum (PM(1)) and coarse PM (PM(10) - PM(1)). Blood samples were collected from each subject on the first (baseline) and last (postexposure) day of a 4-day work week. We analyzed differences between baseline and postexposure levels using a paired Student's t-test. We fitted multivariate mixed-regression models to estimate the associations of interquartile range PM(1) and coarse PM exposure with parameter levels. RESULTS: None of the parameters showed any significant changes from baseline in postexposure samples. However, exposure levels were associated with shorter PT (beta[PM(1)] = -0.33 s, P = 0.08; beta[PM(coarse)] = - 0.33 s, P = 0.01), and higher ETP without exogenous triggers and with thrombomodulin (beta[PM(1)] = + 99 nm min, P = 0.02; beta[PM(coarse)] = + 66 nm min, P = 0.05), t-PA (beta[PM(1)] = + 0.72 ng mL(-1), P = 0.01; beta[PM(coarse)] = + 0.88 ng mL(-1), P = 0.04), and CRP (beta[PM(1)] = + 0.59 mg L(-1), P = 0.03; beta[PM(coarse)] = + 0.48 mg L(-1), P = 0.01). CONCLUSIONS: PM exposure did not show any short-term effect within the week of the study. The association of PM exposure with PT, ETP and CRP provides some evidence of long-term effects on inflammation and coagulation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inflamação/induzido quimicamente , Exposição por Inalação , Metalurgia , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional , Material Particulado/efeitos adversos , Aço/efeitos adversos , Trombofilia/induzido quimicamente , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Inflamação/sangue , Mediadores da Inflamação/sangue , Itália , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/sangue , Tempo de Tromboplastina Parcial , Tamanho da Partícula , Tempo de Protrombina , Análise de Regressão , Medição de Risco , Fatores de Risco , Trombina/metabolismo , Trombofilia/sangue , Fatores de Tempo , Ativador de Plasminogênio Tecidual/sangue
20.
Dig Liver Dis ; 41(11): 817-22, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19467940

RESUMO

BACKGROUND: Cystic fibrosis is the most common lethal recessive disorder among Caucasians. Over 1500 mutations have been identified in cystic fibrosis transmembrane conductance regulator disease-gene so far. A large variability of the clinical phenotype has been observed both in cystic fibrosis patients bearing the same genotype, and in affected sibpairs. Thus, genes inherited independently from cystic fibrosis transmembrane conductance regulator could modulate the clinical expression of cystic fibrosis. METHODS: We analysed some putative modifier genes of liver cystic fibrosis phenotype (serpin 1, hemochromatosis, transferrin receptor 2, ferroportin 1, mannose binding lectin and adenosine triphospate-binding cassette subfamily B member 4) in 108 unrelated cystic fibrosis patients with and without liver involvement. RESULTS: HYPD mannose binding lectin haplotype was significantly (p<0.05) more frequent in cystic fibrosis patients with liver disease versus those without liver disease. This haplotype already related to a more severe pulmonary cystic fibrosis phenotype, is associated to a reduced MBL immunological activity. The c.834-66G>T variant of adenosine triphospate-binding cassette subfamily B member 4 gene was significantly (p<0.05) less frequent in cystic fibrosis patients with liver disease as compared to those with no liver disease. CONCLUSIONS: The HYPD mannose binding lectin haplotype may predispose a subgroup of cystic fibrosis patients to a more severe liver involvement impairing the local defence mechanisms whereas the c.834-66G>T adenosine triphospate-binding cassette subfamily B member 4 variant may enhance the activity of the protein and thus exert a protective effect toward liver disease.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Fibrose Cística/genética , Hepatopatias/genética , Lectina de Ligação a Manose/genética , Adolescente , Adulto , Fibrose Cística/complicações , Feminino , Haplótipos , Humanos , Hepatopatias/complicações , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Adulto Jovem
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