A recent study (Nature Genetics 2014; doi:10.1038/ng.3033 -thanks to Seth Marcus for this reference) provides novel in-depth molecular and mechanistic information on eosinophilic esophagitis (EoE). Though the publication and supplemental material span only 8 pages, it is packed with information and highly technical assays and thus takes an effort to work through.
The authors performed a genome-wide association study (GWAS) of SNPs (single nucleotide polymorphisms) from >1.5 million genetic markers. In total, this study involved samples from 736 EoE patients and 9246 controls. Four prominent markers were identified at 2p23, 5q22, 8p23, adn 15q13; however, the marker at 2p23 was most highly associated with a risk for EoE. And, 2p23 included the CAPN14 gene (best SNP rs77569859).
- CAPN14 is “specifically expressed in esophageal epithelium and is dynamically upregulated as a function of disease activity.” Though CAPN14 is expressed in other tissues, it is primarily in the esophagus and pharynx (Figure 2).
- CAPN14 encodes calpain 14, a calcium-activated cysteine protease. CAPN14 showed the greatest upregulation in comparison to all members of the CAPN family. Calpain proteases mediate protein cleavage for structural proteins, signaling molecules, transcription factors, and inflammatory mediators. The latter are “germane for allergic responses.”
- CAPN14 levels are >2-fold increase in individuals with active EoE.
- CAPN14 gene is modified by IL-13.
Take-home message: (from the authors) This study shows the “potential centrality of CAPN14 in the etiology of EoE….We propose a model that links the interplay of allergic sensitization with an EoE-specific, IL-13-inducible esophageal response involving CAPN14.”
Related blog posts:
- MicroRNA signature for eosinophilic esophagitis …
- Eosinophilic Esophagitis Slide Set | gutsandgrowth
- How Common is Eosinophilic Esophagitis? | gutsandgrowth