PMID- 30819277
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20200323
IS  - 1539-6304 (Electronic)
IS  - 1088-5412 (Linking)
VI  - 40
IP  - 2
DP  - 2019 Mar 1
TI  - Genetics/epigenetics/allergy: The gun is loaded ... but what pulls the trigger?
PG  - 76-83
LID - 10.2500/aap.2019.40.4205 [doi]
AB  - Background: The allergic diseases comprise a group of chronic inflammatory 
      conditions that display a broad spectrum of clinical manifestations primarily 
      mediated by immunoglobulin E (IgE). The prevalence and severity of these 
      IgE-mediated allergic disorders have increased dramatically over the past few 
      decades and are becoming a global health problem. Although genetics plays an 
      important role in determining who develops these atopic disorders, genetics alone 
      cannot fully explain this rapid growth. Results of numerous studies have 
      indicated that epigenetics plays a major pathogenetic role by superimposing its 
      effects above the DNA primal genetic molecule through interactions with and 
      between various susceptibility genes, immunologic influences, and environmental 
      factors. Objective: In this article, the importance and relationships of genetics 
      and epigenetics to an understanding of the immune system in health and in disease 
      were reviewed together with the principles and mechanisms that underlie these 
      entities and which relate to clinical allergy practice. A specific focus of the 
      article was directed to the recent recognition that the IgE-driven atopic 
      disorders are driven by aberrant immune responses in which CD25(+) Forkhead box 
      P3(+) (FoxP3(+)) T-regulatory (Treg) cells that normally suppress inflammatory 
      events are often poorly functioning. Methods: Based on our previous published 
      findings that methylated DNA CpG (cytosine [C], phosphate [p], guanine [G]) 
      oligonucleotide (ODN) but not unmethylated CpG ODN sequence was shown to promote 
      FoxP3 expression in human CD4(+) T cells, the article reviewed the application of 
      DNA methylation and Treg induction to cancer, autoimmune diseases, and the 
      allergic disorders. Results: The central unifying theme of DNA methylation 
      epigenetic mechanism is its comparative description to an electronic "switch," 
      which, when in the methylated state functions in the "closed" position with gene 
      silencing, genome stability, and decreased gene expression, whereas DNA 
      hypomethylation is analogous to the "opened" position of the switch, which leads 
      to active transcription and increased gene expression. Conclusion: Of the three 
      epigenetic mechanisms that include DNA methylation, covalent posttranslational 
      histone modifications, and micro-RNA-mediated gene silencing, DNA methylation 
      plays the major role in understanding mechanisms involved in allergy and 
      immunotherapy. Epigenetics holds the key to unraveling the complex associations 
      between disease phenotypes and endotypes, identifying safer and effective 
      therapies, and creating a better diagnosis and treatment of allergic diseases. 
      Genetics loads the gun and epigenetics pulls the trigger.
FAU - Bellanti, Joseph A
AU  - Bellanti JA
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Allergy Asthma Proc
JT  - Allergy and asthma proceedings
JID - 9603640
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - *DNA Methylation
MH  - *Epigenesis, Genetic
MH  - Humans
MH  - Hypersensitivity/*genetics/immunology/pathology
MH  - Immunoglobulin E/immunology
MH  - T-Lymphocytes, Regulatory/immunology
EDAT- 2019/03/02 06:00
MHDA- 2020/03/24 06:00
CRDT- 2019/03/02 06:00
PHST- 2019/03/02 06:00 [entrez]
PHST- 2019/03/02 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
AID - 10.2500/aap.2019.40.4205 [doi]
PST - ppublish
SO  - Allergy Asthma Proc. 2019 Mar 1;40(2):76-83. doi: 10.2500/aap.2019.40.4205.