scholarly journals DNA Methylation at Birth is Associated with Childhood Serum Immunoglobulin E Levels

2021 ◽  
Vol 14 ◽  
pp. 251686572110081
Author(s):  
Luhang Han ◽  
Akhilesh Kaushal ◽  
Hongmei Zhang ◽  
Latha Kadalayil ◽  
Jiasong Duan ◽  
...  

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.

2017 ◽  
Vol 8 (3) ◽  
pp. ar.2017.8.0207
Author(s):  
Mai Aly Gharib Aly ◽  
Mohamed Tawfik El Tabbakh ◽  
Waheed Fawzy Heissam ◽  
Said Hamed Abbadi

Introduction Allergic rhinitis (AR) is one of the most common allergic diseases, which affects ~20% of the world's population. T-helper (Th) type 2 cells produce interleukin (IL) 4 and IL-13, and mediate allergic responses, and these cytokines have been extensively studied as key players in the atopic airway diseases. However, the involvement of Th17 cells and IL-17 in AR has not been clearly examined. Aim To reevaluate AR clinical severity with serum IL-17, whether IL-17 affects the disease alone or in contribution with the atopic predisposition. Patients and Methods During an 18-month period, 39 individuals were divided into three groups: A, (13 control), B (13 with mild-to-moderate AR), and C (13 with severe AR). Both group B and group C patients (26) were subjected to clinical examination and allergy skin testing, and to measurement of both total serum immunoglobulin E (IgE) and IL-17 levels. Eleven patients with AR then were exposed to 6 months of cluster immunotherapy, whereas the rest of the patients were not exposed. Results Revealed a significant elevation of serum IL-17 levels with an associated increase in serum IgE in the patients with AR compared with controls and revealed that the serum levels of both total serum IgE and IL-17 decreased significantly after cluster immunotherapy. Conclusion These preliminary results added new data about the use of injective immunotherapy as well as reported on the use of sublingual immunotherapy.


2017 ◽  
Vol 21 (6) ◽  
pp. 813-817 ◽  
Author(s):  
Jae-June Dong ◽  
Jay J Shen ◽  
Yong-Jae Lee

Abstract Background Smoking is one of the risk factors to exacerbate allergic diseases, and it may affect serum immunoglobulin E (IgE) levels. However, few studies have relied on an objective biomarker to examine the effect of tobacco smoking on serum IgE levels. Method A nationwide cross-sectional study was conducted to examine the relationship between urinary cotinine (Ucot) concentrations and IgE levels in 973 males using data from the 2010 Korean National Health and Nutrition Examination Survey (KNHANES). Ucot was classified into four groups based on concentration (ng/mL) as follows: nonsmoker group (Ucot &lt;50 ng/mL) and three tertile groups in smokers (T1 [Ucot: 50.00–921.28 ng/mL]; T2 [Ucot: 921.29–1869.36 ng/mL]; and T3 [Ucot ≥1869.37 ng/mL]). The dose-response relationships between Ucot concentrations and total serum IgE level were estimated using analysis of covariance (ANCOVA) and multiple linear regression analysis after adjusting for confounding variables. Results We found a significant and positive dose-related effect of cigarette smoking as measured by Ucot concentrations on the total serum IgE level. The multivariate adjusted means of total serum IgE levels (SE) were 321.0 (36.3), 404.4 (102.7), 499.2 (79.2), and 534.7 (82.7) IU/mL, after adjusting for age, body mass index, alcohol ingestion, physical exercise, job, and household income. The regression coefficient β for total serum IgE was β = 68.6 with increasing level of Ucot group after adjusting for the same covariables (p = .009). Conclusion These findings suggest that the amount of smoking may have a dose-dependent effect on total serum IgE levels. Implication Smoking is one of the risk factors to exacerbate allergic diseases, and it may affect serum immunoglobulin E (IgE) levels, which is closely related to type 1 mediated allergic diseases. However, few studies have relied on an objective biomarker to examine the effect of tobacco smoking on serum IgE levels. We found that tobacco exposure, as measured by Ucot concentrations, increased the serum IgE levels in a dose-response manner in a representative sample of Korean adult males.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chiara Moccia ◽  
Maja Popovic ◽  
Elena Isaevska ◽  
Valentina Fiano ◽  
Morena Trevisan ◽  
...  

Abstract Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Monica del C. Gomez-Alonso ◽  
Anja Kretschmer ◽  
Rory Wilson ◽  
Liliane Pfeiffer ◽  
Ville Karhunen ◽  
...  

Abstract Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.


Allergy ◽  
2009 ◽  
Vol 64 (9) ◽  
pp. 1327-1332 ◽  
Author(s):  
C.-M. Chen ◽  
S. Weidinger ◽  
N. Klopp ◽  
S. Sausenthaler ◽  
W. Bischof ◽  
...  

Epigenomics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 701-713 ◽  
Author(s):  
Ali Altıntaş ◽  
Rhianna C Laker ◽  
Christian Garde ◽  
Romain Barrès ◽  
Juleen R Zierath

Aim: Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. Materials & methods: We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. Results: We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with Gene Ontology terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Conclusion: Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.


2020 ◽  
Vol 7 (1) ◽  
pp. 5-9
Author(s):  
Dr. Mayank Surana ◽  
Dr. Vineeta Pande ◽  
Dr. Sharad Agarkhedkar ◽  
Dr. Ajit Teegala

Allergy, is a clinical expression of soluble factors like IgE, histamine or eosinophils found in serum or plasma of such patients. The products that are responsible for allergy are called as Allergens. Allergens normally induce IgE production which leads to type 1 hypersensitivity response on subsequent exposure to the same allergen. The target organs are mostly nose, lung, skin and gastrointestinal tract. Atopy is also considered as a triad of Atopic dermatitis, allergic rhinitis and bronchial asthma. Raised serum IgE and AEC are proven indicators of allergic phenomenon. Various studies show relationship between serum Immunoglobulin E level and total eosinophil count in population suffering from allergic diseases. Serum total Immunoglobulin E, total eosinophil count and specific IgE are all helpful for the diagnosis and treatment of allergic diseases. Objectives: 1.To Evaluate Serum Total IgE level in Children with allergic diseases.2. To Evaluate Absolute Eosinophil Count (AEC) in children with allergic diseases.3. To Correlate Serum Total Immunoglobulin E Level and Absolute Eosinophil Count (AEC) with allergic diseases. Methodology: Cross sectional study with 100 children in the age group 2-12 years with nasopharyngeal allergies (like bronchial asthma and atopic rhinitis) and skin allergies (like atopic dermatitis, urticaria) ,eye allergies were enrolled and serum IgE levels and AEC levels was done. Results: In present study Absolute eosinophil count was raised in 58% of cases Serum IgE was raised in 54% of cases. In present study, of 58% cases with raised Absolute eosinophil count 81% (47 cases) showed raised serum IgE levels. Conclusion: Absolute eosinophil count and serum Total IgE has been considered as a significant marker of allergic state and can be used as a marker of allergic response in atopic individuals. Raised serum IgE and AEC are more in nasobronchial allergy as compare to other systemic allergies. The elevated level of serum Total IgE and Absolute Eosinophil Count both shows Significant Correlation thus can be considered as a dependable laboratory investigation in diagnosing and categorizing allergic diseases.


2021 ◽  
Author(s):  
Dongrui Zhou ◽  
Na Li ◽  
Fan Yang ◽  
Honglin Zhang ◽  
Zhimao Bai ◽  
...  

Abstract Background Traditional farm environments provide protection from allergic diseases. In this study, farm environmental factors were classified into three categories: environmental microbes, soil, and organic matter. To explore the impact of soil and environmental microorganisms on gut microbiota and immune function, mice were fed sterilized soil, soil microbes (in lieu of environmental microbes), or non-sterilized soil. Results Metagenomic sequencing results showed that the intake of sterile soil while inhaling a small amount of soil microbes in the air, increased gut microbial diversity and the abundance of type III secretion system (T3SS) genes and decreased total serum IgE levels induced by 2-4-dinitrofluorobenzene. The intake of soil microbes increased the abundance of genes involved in the metabolism of short-chain fatty acids and amino acid biosynthesis. By contrast, the intake of soil increased gut microbial diversity, the abundance of T3SS genes and related infectious elements, and genes associated with the metabolism of short-chain fatty acids and amino acid biosynthesis and decreased serum IgE levels. The immune function was positively and significantly correlated with the bacterial secretion system genes, especially with that of T3SS. Conclusions An important mechanism through which farm environments exert a protective effect against allergic diseases could be by serving as a “prebiotic” promoting the reproduction and growth of some intestinal microorganisms that harbor bacterial secretion system genes, especially those of T3SS, whose abundance was positively and significantly correlated with innate immune function of mice.


2021 ◽  
Author(s):  
David M. Howard ◽  
Oliver Pain ◽  
Ryan Arathimos ◽  
Miruna C. Barbu ◽  
Carmen Amador ◽  
...  

AbstractThe environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes in adulthood are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive data on genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27 × 10 −9). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35 × 10−8). Genes and gene-sets annotated from associated CpGs sites and methylation profile scores were then used to quantify any overlap between the early life environment and mental health traits. However, there was no evidence of any overlap after applying a correction for multiple testing. Time of year of birth was found to be associated with a significant difference in estimated lymphocyte and neutrophil counts. Early life environments influence the risk of developing mental health disorders later in life; however, this study provides no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.


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