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

Han, Luhang; Kaushal, Akhilesh; Zhang, Hongmei; Kadalayil, Latha; Duan, Jiasong; Holloway, John W.; Karmaus, Wilfried; Banerjee, Pratik; Tsai, Shih-Fen; Wen, H. Joseph; Arshad, Syed Hasan; Wang, Shu Li

doi:10.1177/25168657211008108

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…26 Exposure to arsenic during pregnancy has been associated with a DNA methylation pattern in infants 27 as well as changes in children's immunoglobulin E levels. 28 Although metals other than arsenic (ie, cadmium, lead, cobalt, copper, nickel, thallium, and zinc)…”

Section: Discussionmentioning

confidence: 99%

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Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan

et al. 2021

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IMPORTANCEThe prevalence of atopic dermatitis has substantially increased in recent decades, and atopic dermatitis could lead to allergic airway inflammation later in life. A previous study found that inorganic arsenic exposure was associated with allergic airway inflammation in children aged 8 to 14 years. However, the association between prenatal exposure to arsenic and other metals and the risk of atopic dermatitis among young children remains unknown. OBJECTIVETo assess the association between prenatal exposure to arsenic and other metals and the occurrence of atopic dermatitis in children at age 4 years. DESIGN, SETTING, AND PARTICIPANTS In total, 1152 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 586 mothers and children aged 4 years participated in follow-up questionnaire interviews from August 2016 to January 2019. After excluding 216 participants with missing data, the final statistical analysis of follow-up data included 370 mother and child pairs from the central and eastern regions of Taiwan. Data were analyzed from February 2 to August 12, 2021.EXPOSURES Arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc during pregnancy. MAIN OUTCOMES AND MEASURESThe outcome was parent-reported atopic dermatitis history among children aged 4 years. The presence of atopic dermatitis was defined as a positive response to the question, "Has your child ever had atopic dermatitis diagnosed by a physician?" During the initial TMICS study period, concentrations of arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc were measured in maternal urine during the third trimester of pregnancy using an inductively coupled plasma mass spectrometer. Estimated total inorganic arsenic exposure was calculated using a model that included data on both total arsenic and arsenic species (arsenite, arsenate, monomethylarsonate, and dimethylarsenate) obtained from a previous TMICS cohort. RESULTS Among 370 children included in the analysis, the mean (SD) age was 3.94 (0.59) years; 208 children (56.2%) were male, and 267 children (72.2%) were from the central region of Taiwan.A total of 110 children (29.7%) had atopic dermatitis at age 4 years. Maternal estimated total inorganic arsenic exposure during pregnancy was associated with increased odds of atopic dermatitis among children at age 4 years (odds ratio [OR], 2.42 [95% CI, for every doubled increase of total inorganic arsenic) after adjusting for parental allergies, child's sex, geographic area, maternal educational level, and exposure to tobacco smoke. Every increased unit in the weighted quantile sum index of maternal metal exposure was significantly associated with atopic dermatitis (OR, 1.63; 95% CI, 1.28-2.07). Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal mixture index. (continued) Key Points Question Is prenatal exposure to arsenic an...

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Section: Discussionmentioning

confidence: 99%

“… 26 Exposure to arsenic during pregnancy has been associated with a DNA methylation pattern in infants 27 as well as changes in children’s immunoglobulin E levels. 28 …”

Section: Discussionmentioning

confidence: 99%

Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan

et al. 2021

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“…Environmental and epigenetic factors like DNA methylation, histone modification and microRNA’s can alter the expression of these genes. Studies regarding DNA methylation changes in cytokine genes such as interferon gamma (IFN-γ), interleukin-4 (IL-4) and IL-5 and in Forkhead box P3 (FoxP3) indicate that changes in DNA methylation may predispose IgE-mediated food sensitization or allergy in early childhood ( 35 – 38 ). Acevedo et al studied the DNA methylation levels in mononuclear leukocytes from mothers and their children.…”

Section: Immunological Changes In Early Solid Food Introduction In Th...mentioning

confidence: 99%

The clinical and immunological basis of early food introduction in food allergy prevention

et al. 2023

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IgE-mediated food allergy has an estimated prevalence of 6%–10% in developed countries. Allergen avoidance has long been the main focus in the prevention of food allergy and late solid food introduction after 6–12 months of age was recommended in high-risk infants. However, the rising prevalence of food allergy despite delayed exposure to allergens and the observations that IgE-mediated sensitization to food products could even occur before the introduction of solid foods resulted in a shift towards early solid food introduction as an attempt to prevent IgE-mediated food allergy. Since then, many trials focused on the clinical outcome of early allergen introduction and overall seem to point to a protective effect on the development of IgE-mediated food allergies. For non-IgE-mediated diseases of food allergy, evidence of early food introduction seems less clear. Moreover, data on the underlying immunological processes in early food introduction is lacking. The goal of this review is to summarize the available data of immunological changes in early food introduction to prevent IgE and non-IgE mediated food allergy.

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“…However, the predictive capabilities in prospective associations with aeroallergen sensitization were limited, indicating that DNAm might be a result rather than a predictor of allergic sensitization. On the other hand, studies investigating DNAm in cord-blood found associations with higher IgE levels later in life [ 8 , 9 ], indicating a certain predictive potential.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation and aeroallergen sensitization: The chicken or the egg?

et al. 2022

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Background DNA methylation (DNAm) is considered a plausible pathway through which genetic and environmental factors may influence the development of allergies. However, causality has yet to be determined as it is unknown whether DNAm is rather a cause or consequence of allergic sensitization. Here, we investigated the direction of the observed associations between well-known environmental and genetic determinants of allergy, DNAm, and aeroallergen sensitization using a combination of high-dimensional and causal mediation analyses. Methods Using prospectively collected data from the German LISA birth cohort from two time windows (6–10 years: N = 234; 10–15 years: N = 167), we tested whether DNAm is a cause or a consequence of aeroallergen sensitization (specific immunoglobulin E > 0.35kU/l) by conducting mediation analyses for both effect directions using maternal smoking during pregnancy, family history of allergies, and a polygenic risk score (PRS) for any allergic disease as exposure variables. We evaluated individual CpG sites (EPIC BeadChip) and allergy-related methylation risk scores (MRS) as potential mediators in the mediation analyses. We applied three high-dimensional mediation approaches (HIMA, DACT, gHMA) and validated results using causal mediation analyses. A replication of results was attempted in the Swedish BAMSE cohort. Results Using high-dimensional methods, we identified five CpGs as mediators of prenatal exposures to sensitization with significant (adjusted p < 0.05) indirect effects in the causal mediation analysis (maternal smoking: two CpGs, family history: one, PRS: two). None of these CpGs could be replicated in BAMSE. The effect of family history on allergy-related MRS was significantly mediated by aeroallergen sensitization (proportions mediated: 33.7–49.6%), suggesting changes in DNAm occurred post-sensitization. Conclusion The results indicate that DNAm may be a cause or consequence of aeroallergen sensitization depending on genomic location. Allergy-related MRS, identified as a potential cause of sensitization, can be considered as a cross-sectional biomarker of disease. Differential DNAm in individual CpGs, identified as mediators of the development of sensitization, could be used as clinical predictors of disease development. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-022-01332-5.

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

Cited by 11 publications

References 42 publications

Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan

Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan

The clinical and immunological basis of early food introduction in food allergy prevention

DNA methylation and aeroallergen sensitization: The chicken or the egg?

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