BackgroundIn utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence in later life.MethodsGenome-wide DNA methylation in cord blood from 64 subjects in the Taiwanese maternal infant and birth cohort was analyzed. Robust regressions were applied to assess the association of DNA methylation with in utero arsenic exposure. Multiple testing was adjusted by controlling false discovery rate (FDR) of 0.05. The DAVID bioinformatics tool was implemented for functional annotation analyses on the detected CpGs. The identified CpGs were further tested in an independent cohort. For the CpGs replicated in the independent cohort, linear mixed models were applied to assess the association of DNA methylation with low-density lipoprotein (LDL) at different ages (2, 5, 8, 11 and 14 years).ResultsIn total, 579 out of 385,183 CpGs were identified after adjusting for multiple testing (FDR = 0.05), of which ~60% were positively associated with arsenic exposure. Functional annotation analysis on these CpGs detected 17 KEGG pathways (FDR = 0.05) including pathways for cardiovascular diseases (CVD) and diabetes mellitus. In the independent cohort, about 46% (252 out of 553 CpGs) of the identified CpGs showed associations consistent with those in the study cohort. In total, 11 CpGs replicated in the independent cohort were in the pathways related to CVD and diabetes mellitus. Via longitudinal analyses, we found at 5 out of the 11 CpGs methylation was associated with LDL over time and interactions between DNA methylation and time were observed at 4 of the 5 CpGs, cg25189764 (coeff = 0.157, p-value = 0.047), cg04986899 (coeff. For interaction [coeff.int] = 0.030, p-value = 0.024), cg04903360 (coeff.int = 0.026, p-value = 0.032), cg08198265 (coeff.int = −0.063, p-value = 0.0021), cg10473311 (coeff.int = −0.021, p-value = 0.027).ConclusionIn utero arsenic exposure was associated with cord blood DNA methylation at various CpGs. The identified CpGs may help determine pathological epigenetic mechanisms linked to in utero arsenic exposure. Five CpGs (cg25189764, cg04986899, cg04903360, cg08198265 and cg10473311) may serve as epigenetic markers for changes in LDL later in life.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-017-0262-0) contains supplementary material, which is available to authorized users.
Immunoglobulin E (IgE) is known to play an important role in allergic diseases. Epigenetic traits acquired due to modification of deoxyribonucleic acid (DNA) methylation (DNAm) in early life may have phenotypic consequences through their role in transcriptional regulation with relevance to the developmental origins of diseases including allergy. However, epigenome-scale studies on the longitudinal association of cord blood DNAm with IgE over time are lacking. Our study aimed to examine the association of DNAm at birth with childhood serum IgE levels during early life. Genome-scale DNAm and total serum IgE measured at birth, 5, 8, and 11 years of children in the Taiwan Maternal and Infant Cohort Study were included in the study in the discovery stage. Linear mixed models were implemented to assess the association between cord blood DNAm at ~310K 5′-cytosine-phosphate-guanine-3′ (CpG) sites with repeated IgE measurements, adjusting for cord blood IgE. Identified statistically significant CpGs (at a false discovery rate, FDR, of 0.05) were further tested in an independent replication cohort, the Isle of Wight (IoW) birth cohort. We mapped replicated CpGs to genes and conducted gene ontology analysis using ToppFun to identify significantly enriched pathways and biological processes of the genes. Cord blood DNAm of 273 CpG sites were significantly (FDR = 0.05) associated with IgE levels longitudinally. Among the identified CpGs available in both cohorts (184 CpGs), 92 CpGs (50%) were replicated in the IoW in terms of consistency in direction of associations between DNA methylation and IgE levels later in life, and 16 of the 92 CpGs showed statistically significant associations ( P < .05). Gene ontology analysis identified 4 pathways (FDR = 0.05). The identified 16 CpG sites had the potential to serve as epigenetic markers associated with later IgE production, beneficial to allergic disease prevention and intervention.
Postmortem proteolysis of breast (BM) and leg (LM) muscles from Taiwan colored chickens (TCC) and silkie bantams (SB) at 5°C were compared. Myofibrils were prepared from BM and LM samples that were randomly taken from the carcasses of SB and TCC after 0, 1, 3, 7 and 14 days of storage at 5°C. pH of samples was determined, and degradation of myofibrillar proteins was analyzed by the SDS-PAGE and western blots. The results showed that pH was lower in BM than in LM samples from both avian strains. Appearance of 30 kDa components and disappearance of titin and nebulin were more rapidly as seen on SDS-PAGE in BM than in LM samples. Western blots labeled with a monoclonal antibody to desmin also demonstrated that desmin degraded more quickly in BM samples. Our data might suggest that postmortem proteolysis occurred more rapidly in BM than in LM from both TCC and SB.
Prenatal exposure to heavy metals may cause atopic diseases. Little association between cord blood total immunoglobulin E (CB‐tIgE) levels and the occurrence of atopic diseases has been found. This study investigated the atopic status and tIgE trajectory trend in a Taiwanese birth cohort over 15 years. We also assessed the effect of maternal heavy metal exposure on maternal serum cytokine and CB‐tIgE levels. We recruited 430 pregnant women during their third trimester in 2000–2001. Maternal urinary heavy metal concentrations and serum cytokine levels were measured. The CB‐tIgE and serum tIgE levels of the women’s children when they were aged 5, 8, 11, and 14 years were measured. The upper quartile of the maternal urinary arsenic concentration was associated with an increased risk of a CB‐tIgE level higher than 1 IU/mL (odds ratio, 1.845; 95% confidence interval, 1.003–3.395). Serum tIgE trajectory levels were the highest in children with asthma, followed by those with atopic dermatitis and allergic rhinitis at the age of 5–14 years. Serum tIgE levels tended to peak at the age of 11 years in the atopic children but were stable from the age of 8 years in the non‐atopic children. We first demonstrated that serum tIgE levels reached a trajectory peak in the atopic children aged 11 years. Prenatal exposure to arsenic may increase the risk of elevated CB‐tIgE levels. Further investigation is warranted to elucidate the mechanism through which maternal serum cytokines affect the occurrence of atopic diseases in children.
Background Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel‐induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. Objectives We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. Methods Using a birth cohort study, we analysed 140 mother–child pairs recruited in 2012–2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP‐MS). The serum levels of 65 analytes and IgE in 3‐year‐old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. Results The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 μg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL‐1β, IL‐2, TNF‐α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase‐1 (MMP‐1), IL‐2R, and eotaxin‐1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL‐2R, but it was negatively associated with the maternal nickel exposure. Conclusions This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.
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