Abstract
Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the accumulation of eosinophils in the esophagus. We report association of EoE with variants at chromosome 5q22 encompassing TSLP and WDR36 (rs3806932, combined P = 3.19 × 10−9). TSLP is overexpressed in esophageal biopsies from individuals with EoE compared with unaffected individuals, whereas WDR36 expression is unaltered between the two groups. These data implicate the 5q22 locus in the pathogenesis of EoE and identify TSLP as the most likely candidate gene in the region.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Furuta, G.T. et al. Gastroenterology 133, 1342–1363 (2007).
Spergel, J.M., Brown-Whitehorn, T., Beausoleil, J.L., Shuker, M. & Liacouras, C.A. J. Allergy Clin. Immunol. 119, 509–511 (2007).
Akei, H.S., Mishra, A., Blanchard, C. & Rothenberg, M.E. Gastroenterology 129, 985–994 (2005).
Noel, R.J., Putnam, P.E. & Rothenberg, M.E. N. Engl. J. Med. 351, 940–941 (2004).
Collins, M.H. et al. Clin. Gastroenterol. Hepatol. 6, 621–629 (2008).
Malerba, G. et al. Am. J. Respir. Crit. Care Med. 162, 1587–1590 (2000).
Blanchard, C. et al. J. Clin. Invest. 116, 536–547 (2006).
Challa, P. Int. Ophthalmol. Clin. 48, 73–94 (2008).
Liu, Y.J. Adv. Immunol. 101, 1–25 (2009).
Oyoshi, M.K., He, R., Kumar, L., Yoon, J. & Geha, R.S. Adv. Immunol. 102, 135–226 (2009).
Blanchard, C. et al. J. Allergy Clin. Immunol. 120, 1292–1300 (2007).
Tonozuka, Y. et al. Cytogenet. Cell Genet. 93, 23–25 (2001).
Gudbjartsson, D.F. et al. Nat. Genet. 41, 342–347 (2009).
Konikoff, M.R. et al. Clin. Gastroenterol. Hepatol. 4, 1328–1336 (2006).
Acknowledgements
We thank all of the participating families and subjects. We thank B. Buckmeier, A. Ahrens, S. Jameson, M. Palazzolo, H. Foote, M. Mingler, M. Shuker and E. Stucke for assistance with patient enrollment, DNA preparation and/or database management. This work was supported in part by US National Institutes of Health (NIH) U19 AI070235, NIH R01 DK076893, Food Allergy Project, Campaign Urging Research for Eosinophilic Disorders (CURED) Foundation, American Partnership for Eosinophilic Disorders (APFED), The Children's Hospital of Philadelphia Chair's Institutive, the Buckeye Foundation and the Coltswold Foundation. All genome-wide genotyping was funded by an Institute Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia.
Author information
Authors and Affiliations
Contributions
M.E.R., J.M.S., S.A., M.H.C., T.B.-W., P.E.P., J.P.F., S.F.A.G., J.P.A., P.M.A.S. and H.H. designed the study. J.M.S., J.D.S., L.J.M., A.C., L.G., C.K., J.G., E.F., K.T., C.B., C.L., R.V., R.M.C. and H.H. generated the data. K.A., J.D.S., L.J.M. and P.M.A.S. analyzed the data. M.E.R., J.M.S., J.D.S., P.M.A.S. and H.H. prepared the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures
Supplementary Methods, Supplementary Figures 1–4 and Supplementary Tables 1 and 2 (PDF 3048 kb)
Rights and permissions
About this article
Cite this article
Rothenberg, M., Spergel, J., Sherrill, J. et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet 42, 289–291 (2010). https://doi.org/10.1038/ng.547
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng.547
This article is cited by
-
Association of Eosinophilic Esophagitis and Human Immunodeficiency Virus
Digestive Diseases and Sciences (2021)
-
Sleep in children with eosinophilic esophagitis
World Journal of Pediatrics (2021)
-
A FACS-based approach to obtain viable eosinophils from human adipose tissue
Scientific Reports (2020)
-
TGFβ1 single-nucleotide polymorphism C-509T alters mucosal cell function in pediatric eosinophilic esophagitis
Mucosal Immunology (2020)
-
Relationship Between Housing Components and Development of Eosinophilic Esophagitis
Digestive Diseases and Sciences (2020)