Genetics and epigenetics of allergy

Abstract

Purpose of review Allergic diseases are prototypic examples for gene × environment-wide interactions. This review considers the current evidence for genetic and epigenetic mechanisms in allergic diseases and highlights barriers and facilitators for the implementation of these novel tools both for research and clinical practice. Recent findings The value of whole-genome sequencing studies and the use of polygenic risk score analysis in homogeneous well characterized populations are currently being tested. Epigenetic mechanisms are known to play a crucial role in the pathogenesis of allergic disorders, especially through mediating the effects of the environmental factors, well recognized risk modifiers. There is emerging evidence for the immune-modulatory role of probiotics through epigenetic changes. Direct or indirect targeting of epigenetic mechanisms affect expression of the genes favouring the development of allergic diseases and can improve tissue biology. The ability to specifically edit the epigenome, especially using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, holds the promise of enhancing understanding of how epigenetic modifications function and enabling manipulation of cell phenotype for research or therapeutic purposes. Summary Additional research in the role of genetic and epigenetic mechanisms in relation to allergic diseases’ endotypes is needed. An international project characterizing the human epigenome in relation to allergic diseases is warranted.

Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer

“…GC is a sustained multistep process that involves accumulated genetic damage, altered epigenetic signatures, and exposure to environmental factors. An increasing number of studies have confirmed that epigenetic alterations can mediate the effects of environmental factors on disease ( Agache et al, 2020 ). As the most typical epigenetic alteration, DNA hypermethylation is closely linked to improper transcriptional silencing and the functional loss of genes to accelerate the growth of tumor cells and promote tumorigenesis and development ( Abudurexiti et al, 2020 ).…”

Omics technologies in allergy and asthma research: An EAACI position paper

“…Epigenetic changes can be mitotically (cellular memory) or meiotically (parental imprinting) heritable and can be passed through generations 28 . Interestingly, already the prenatal and early postnatal period can influence the development of diseases such as allergy in adulthood 28,29 . Several recent, epigenomic studies in the field of allergic diseases allowed identification of epigenetic signatures of asthma/allergy and are summarized in Table 50–57 .…”

A pathogenic integrated view explaining the different endotypes of asthma and allergic disorders

“…The human genes involved in IgE response include those controlling the IgE locus and those encoding the HLA class II complex favoring the expansion of allergen‐specific Th2 cells and the IgE switch of B cells. These genes are located in the chromosome (chr) 5 (region 5q23‐35) encoding type‐2 cytokines, chr6 encoding HLA class II alleles and the peptide transport molecules TAP1 and TAP2, chr11 for the high‐affinity Fcε receptor (FcεRI), chr12 for the signal transducer and activator of transcription 6 (STAT6), and chr16 for the IL‐4R α‐chain 24‐26 . Several polymorphisms associated with candidate genes for respiratory allergy have been described, which may vary according to racial diversity 27 .…”

“…These genes are located in the chromosome (chr) 5 (region 5q23-35) encoding type-2 cytokines, chr6 encoding HLA class II alleles and the peptide transport molecules TAP1 and TAP2, chr11 for the high-affinity Fcε receptor (FcεRI), chr12 for the signal transducer and activator of transcription 6 (STAT6), and chr16 for the IL-4R α-chain. [24][25][26] Several polymorphisms associated with candidate genes for respiratory allergy have been described, which may vary according to racial diversity. 27 The principal well-documented genes involved in the genetic alterations in these diseases are listed in Table 1.…”