Genetics and Epigenetics in Allergic Rhinitis
Abstract
:1. Introduction
2. Heredity in AR
Twin Studies
3. Overlapping Genetic Architecture in AR and Asthma
3.1. Genetics of Asthma
3.2. Overlapping Genes in AR and Asthma
4. GWAS in AR
4.1. Previously Known Loci in AR
4.2. Novel Loci Identified in AR
5. Epigenetics in Allergic Rhinitis
6. Future Studies
6.1. Limitation of Current Genetic Studies in AR
6.2. Directions for Future Studies
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chromosome | Gene | Possible Allergic Mechanism | References |
---|---|---|---|
19p13 | MRPL4 | Involved in inflammatory adhesion process. | [61] |
10q24 | BCAP | B cells development, activation, and maturation. | [61] |
11q13 | C11orf30/LRRC32 | Epithelial barrier function, regulatory | [18] |
T-cell function, and immune tolerance. | |||
4p14 | TLR6 | Pattern recognition receptors in innate immunity. | [18] |
4q27 | IL2 | Immune regulatory effects. | [19] |
5q22.1 | TSLP | Th2 immune responses. | [18] |
TMEM232, SLCA25A46 | |||
6p21.32 | HLA region (BTNL2,HLA-DPB1,HLA-DQA1,HLA-DQB1,HLA-DRB1, | Antigen presentation, self tolerance. | [18] |
HLA-DRB3,HLA-DRB4,HLA-DRB5,TAP1, andTAP2) | |||
11q13.5 | C11orf30, LRRC32 | Expressed in regulatory T cell, involved in TGF-β signaling. | [18] |
14q23.1 | PPM1A, DHRS7 | [18] | |
16p13.13 | CLEC16A | Highly expressed in lung, T- and B-cells with unknown function. | [20] |
5p13.2 | CAPSL; IL7R | V(D)J recombination of B and T cell receptors. | [59] |
T cell subtypes have different levels of IL-7R on the cell surface. | |||
12q24.31 | CDK2AP1; C12orf65 | Involved in downstream of T cell receptor activation. Involved in hematopoiesis. | [59] |
6q15 | BACH2; GJA10 | Production of memory T cells and memory B cells induced by antigen. | [59] |
11q23.3 | CXCR5; DDX6 | Chemokine receptor expressed on B cells and involved in B cell migration in spleen and lymph nodes. | [59] |
CXCR5 is expressed on a subset of follicular T cells. | |||
1q23.3 | AL590714.1; FCER1G | Encodes IgE receptor in epithelial cells and immune cells. Tanb | [61] |
15q15.1 | ITPKA; RTF1 | TYRO3 inhibits immune signaling mediated from TLR and activates SOCS1. Leukocyte tyrosine kinase is involved in downstream of T cell receptor activation. | [59] |
4q24 | MANBA; NFKB1 | NFKB1 is involved in activation of inflammatory pathways, mediating signals from TLRs and cytokines. | [82] |
7p15.1 | JAZF1; TAX1BP1 | Transcriptional repressor in endometrial stromal tumors, multiple sclerosis and Th2 diabetes. | [59] |
12q24.12 | ATXN2; SH2B3 | Involved in hematopoiesis and downstream of T cell receptor activation. | [59] |
9q34.2 | ABO; OBP2B | Allele variants of ABO determine blood group type. | [59] |
3p21.2 | VPRBP | Involved in T cell proliferation and V(D)J recombination in B cell development. | [59] |
2p23.2 | FOSL2; RBKS | Cell cycle and proliferation. | [59] |
10q24.32 | ACTR1A; TMEM180 | Subunit of NFKB complex and involved in regulating TLR-4 and cytokine signaling. | [59] |
1p31.1 | LRRIQ3; NEGR1 | Cell adhesion. | [59] |
19q13.11 | CEBPA; SLC7A10 | CEBPG is involved in transcriptional enhancers for the immunoglobulin heavy chain. CEBPA is involved in lung development and inflammatory bowel disease. | [83] |
12q24.31 | SPPL3; ACADS | Regulate the number of NK cells. OASL is involved in IFN-γ signaling. | [59] |
2q36.3 | SPHKAP; DAW1 | Dynein assembly factor. | [59] |
15q22.2 | RORA | Involved in development of natural helper cell. | [84] |
1p36.23 | RERE; SLC45A1 | Apoptosis-associated transcription factor. | [85] |
13q14.11 | TNFSF11; AKAP11 | Help dendritic cells to enhance T cell activation. | [59] |
miRNA | Target | Function | References |
---|---|---|---|
let-7 | JAK1/STAT3, IL-13, SOCS4 | Regulating IL-13 secretion and modulating Th2 inflammation. | [99,109,110] |
miR-206 | S100A7A, VEGF | Involved in the VEGF pathway | [101] |
miR-338-3p | WNT/ β-Catenin | inducing epithelial-mesenchymal transition by inhibition of Wnt/β-catenin pathway. | [101] |
miR-16 | IκB/NF-κB | Prevents IL-13-induced inflammatory cytokine secretion. | [111] |
miR-498 | STAT3 | Suppressing Th17 cell differentiation. | [99,101] |
miR-187 | CD276 | Regulation of T-cell response. | [99,112] |
miR-143 | TGF-β1 | Modulates memory T-cell differentiation. | [99,112] |
miR-886-3p | SMAD3, FoxO1 | Regulates TGF pathway via SMAD3. | [99,112] |
miR-224 | SMAD4 | Regulates TGF pathway via SMAD4. | [99,112] |
miR-155 | IL13Ra1 | Control the proliferation and differentiation of Treg cells and regulates IL-13 pathway in macrophages. | [113,114,115,116] |
miR-126 | VEGF, IRS1 | Decreased expression in mononuclear leukocytes, regulating IL4 effect. | [117] |
miR18a | CTGF | Involved in TGF pathway. | [101] |
miR-205 | MICAL2 | Activation of ERK17 pathway. | [99] |
miR-375 | JAK2/STAT3 | Prevents apoptosis of nasal mucosa cells | [118] |
miR-19a | TGFβ1 | attenuate allergen-induced suppression of IL-10 in the peripheral dendritic cells. | [117] |
miR-26a | SMAD2, SMAD3 | Modulation of TGF-β-dependent signaling pathways and repression of inflammatory responses by promoting regulatory T-cell responses or through NF-κB inhibition. | [101] |
miR-135a | GATA-3 | Increase in the levels of IL-4 and IgE in nasal mucosa, prevent mast cell activation/degranulation. | [119] |
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Choi, B.Y.; Han, M.; Kwak, J.W.; Kim, T.H. Genetics and Epigenetics in Allergic Rhinitis. Genes 2021, 12, 2004. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12122004
Choi BY, Han M, Kwak JW, Kim TH. Genetics and Epigenetics in Allergic Rhinitis. Genes. 2021; 12(12):2004. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12122004
Chicago/Turabian StyleChoi, Bo Yoon, Munsoo Han, Ji Won Kwak, and Tae Hoon Kim. 2021. "Genetics and Epigenetics in Allergic Rhinitis" Genes 12, no. 12: 2004. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12122004