Table 1.
Common risk genes with known functions.
| Genetic Risk Loci | Gene at and Near Risk Variants | p-Value in Case of GWAS Approach (or the Approach Used) | Known Function/Possible Pathogenic Mechanisms |
|---|---|---|---|
| 2p23.1 | CAPN14 | 5 × 10−10 | Encodes a proteolytic enzyme specific to the esophagus that is induced by IL-13 and involved in epithelial homeostasis and repair |
|
CCL26 (/eotaxin-3) |
(candidate gene) | A potent eosinophil chemoattractant and activating factor induced by IL-13 | |
| CRLF2 | (candidate gene) | TSLP receptor | |
| FLG | (candidate gene) | Esophageal barrier function | |
| IL-5/IL-13 | (PheWAS) | Th2 signaling | |
| 11q13.5 |
LRRC32
C11orf30 (EMSY) CAPN5 |
4 × 10−11 | LRRC32 is a TGF-β binding protein. Possibly TFG-β signaling/epithelial protease function/barrier function EMSY is involved in transcriptional regulation |
| 12q13 | STAT6 | 2 × 10−6 | IL-13 responsive transcription factor, Th2 development |
| TGFβ1 | (candidate gene) | Th2 skewing and fibrosis | |
| 5q22.1 |
TSLP
WDR36 |
3 × 10−9 | Potent Th2 skewing Induces Th2 cell development and activates eosinophils and basophils |
| 19q13.11 |
ANKRD27
PDCD5 RGS9BP |
2 × 10−9 | ANKRD27 inhibits the SNARE complex PDCD5 is involved in apoptotic pathways RGS9BP is not expressed in the esophagus or by immune cells |
| 18q12.1 |
DSG1
DCC |
(mapping/sequencing/phenotype association) 7 × 10−6 |
Regulates esophageal epithelial barrier function |
| TGFβR1/TGFβR2/PBN | (phenotype association) | Th2 skewing and fibrosis | |
| PTEN | (phenotype association) | Regulation of eosinophil response | |
| STAT3 | (phenotype association) | Engagement in signal pathway of growth factors, hormones and multiple cytokines | |
| SPINK5 | (phenotype association) | Esophageal barrier function | |
| DOCK8 | (phenotype association) | Potent role in T-cell homeostasis |
GWAS, genome-wide association studies. CAPN14, calpain-14. IL, interleukin. CCL26, chemokine ligand 26. CRLF2, cytokine receptor-like factor 2. TSLP, thymic stromal lymphopoietin. FLG, filaggrin. PheWAS, phenome-wide association studies. LRRC32, leucine-rich repeat containing 32. STAT, signal transducer and activator of transcription. TGFβ, transforming growth factor beta. WDR, WD repeat domain. ANKRD, ankyrin repeat domain. PDCD, programmed cell death. RGS9BP, regulator of G protein signaling 9 binding protein. DSG, desmoglein. DCC, deleted in colorectal cancer. FBN, fibrillin. PTEN, phosphatase and tensin homolog. STAT, signal transducer and activator of transcription. SPINK5, serine protease inhibitor Kazal-type 5. DOCK8, dedicator of cytokinesis 8.