Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Common variants at 5q22 associate with pediatric eosinophilic esophagitis

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

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Regional plot of the 5q22 locus and follow-up expression studies.

Similar content being viewed by others

References

  1. Furuta, G.T. et al. Gastroenterology 133, 1342–1363 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Spergel, J.M., Brown-Whitehorn, T., Beausoleil, J.L., Shuker, M. & Liacouras, C.A. J. Allergy Clin. Immunol. 119, 509–511 (2007).

    Article  PubMed  Google Scholar 

  3. Akei, H.S., Mishra, A., Blanchard, C. & Rothenberg, M.E. Gastroenterology 129, 985–994 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Noel, R.J., Putnam, P.E. & Rothenberg, M.E. N. Engl. J. Med. 351, 940–941 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Collins, M.H. et al. Clin. Gastroenterol. Hepatol. 6, 621–629 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Malerba, G. et al. Am. J. Respir. Crit. Care Med. 162, 1587–1590 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Blanchard, C. et al. J. Clin. Invest. 116, 536–547 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Challa, P. Int. Ophthalmol. Clin. 48, 73–94 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Liu, Y.J. Adv. Immunol. 101, 1–25 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Oyoshi, M.K., He, R., Kumar, L., Yoon, J. & Geha, R.S. Adv. Immunol. 102, 135–226 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Blanchard, C. et al. J. Allergy Clin. Immunol. 120, 1292–1300 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Tonozuka, Y. et al. Cytogenet. Cell Genet. 93, 23–25 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Gudbjartsson, D.F. et al. Nat. Genet. 41, 342–347 (2009).

    Article  CAS  PubMed  Google Scholar 

  14. Konikoff, M.R. et al. Clin. Gastroenterol. Hepatol. 4, 1328–1336 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

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

Authors

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

Correspondence to Hakon Hakonarson.

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

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.547

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing