Targeted DNA methylation profiling reveals epigenetic signatures in peanut allergy

DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing...

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Vydáno v:JCI insight Ročník 6; číslo 6
Hlavní autoři: Zhou, Xiaoying, Han, Xiaorui, Lyu, Shu-Chen, Bunning, Bryan, Kost, Laurie, Chang, Iris, Cao, Shu, Sampath, Vanitha, Nadeau, Kari C.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Society for Clinical Investigation 22.03.2021
American Society for Clinical investigation
Témata:
Allergens
Bisulfite
Brain-derived neurotrophic factor
CpG Islands
Cytokines
Cytokines - immunology
DNA fingerprinting
DNA Methylation
Epigenesis, Genetic
Epigenetics
Food allergies
Gene Expression Profiling
Genes
Genetic factors
Genetics
Humans
Immunology
Innate immunity
Kinases
Lymphocytes T
Mann-Whitney U test
Peanut Hypersensitivity - genetics
Peripheral blood
Proteins
Siblings
Th2 Cells - immunology
Twins
Epigenetics
Allergy
Genetics
Immunology
ISSN:2379-3708, 2379-3708
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Abstract DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) versus nonallergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity), as well as DNAm signature combinations with superior diagnostic potential compared with serum peanut-specific IgE for PA versus NA. Furthermore, we found that, following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared with NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than those in randomly paired genetically unrelated individuals, suggesting that PA-related DNAm signatures may be associated with genetic factors.
AbstractList DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) versus nonallergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity), as well as DNAm signature combinations with superior diagnostic potential compared with serum peanut-specific IgE for PA versus NA. Furthermore, we found that, following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared with NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than those in randomly paired genetically unrelated individuals, suggesting that PA-related DNAm signatures may be associated with genetic factors.DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) versus nonallergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity), as well as DNAm signature combinations with superior diagnostic potential compared with serum peanut-specific IgE for PA versus NA. Furthermore, we found that, following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared with NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than those in randomly paired genetically unrelated individuals, suggesting that PA-related DNAm signatures may be associated with genetic factors.
DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) versus nonallergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity), as well as DNAm signature combinations with superior diagnostic potential compared with serum peanut–specific IgE for PA versus NA. Furthermore, we found that, following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared with NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than those in randomly paired genetically unrelated individuals, suggesting that PA-related DNAm signatures may be associated with genetic factors.
Author Chang, Iris
Sampath, Vanitha
Kost, Laurie
Cao, Shu
Nadeau, Kari C.
Zhou, Xiaoying
Lyu, Shu-Chen
Bunning, Bryan
Han, Xiaorui
AuthorAffiliation Sean N. Parker Center for Allergy & Asthma Research at Stanford University and Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, California, USA
AuthorAffiliation_xml – name: Sean N. Parker Center for Allergy & Asthma Research at Stanford University and Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, California, USA
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  surname: Bunning
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  givenname: Iris
  surname: Chang
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  surname: Nadeau
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33571165$$D View this record in MEDLINE/PubMed
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Issue 6
Keywords Epigenetics
Allergy
Genetics
Immunology
Language English
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Snippet DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study,...
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SubjectTerms Allergens
Bisulfite
Brain-derived neurotrophic factor
CpG Islands
Cytokines
Cytokines - immunology
DNA fingerprinting
DNA Methylation
Epigenesis, Genetic
Epigenetics
Food allergies
Gene Expression Profiling
Genes
Genetic factors
Genetics
Humans
Immunology
Innate immunity
Kinases
Lymphocytes T
Mann-Whitney U test
Peanut Hypersensitivity - genetics
Peripheral blood
Proteins
Siblings
Th2 Cells - immunology
Twins
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Title Targeted DNA methylation profiling reveals epigenetic signatures in peanut allergy
URI https://www.ncbi.nlm.nih.gov/pubmed/33571165
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