Common Variants at 5q22 Associate with Pediatric Eosinophilic Esophagitis

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 Mar 9

PMID 20208534

Citations 227

Authors

Marc E Rothenberg

Jonathan M Spergel

Joseph D Sherrill

Kiran Annaiah

Lisa J Martin

Antonella Cianferoni

Laura Gober

Cecilia Kim

Joseph Glessner

Edward Frackelton

Kelly Thomas

Carine Blanchard

Chris Liacouras

Ritu Verma

Seema Aceves

Margaret H Collins

Terri Brown-Whitehorn

Phil E Putnam

James P Franciosi

Rosetta M Chiavacci

Struan F A Grant

J Pablo Abonia

Patrick M A Sleiman

Hakon Hakonarson

Affiliations

Soon will be listed here.

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 x 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.

Citing Articles

Distinct roles for thymic stromal lymphopoietin (TSLP) and IL-33 in experimental eosinophilic esophagitis.

Dsilva A, Wagner A, Itan M, Rhone N, Avlas S, Gordon Y bioRxiv. 2025; .

PMID: 40060399 PMC: 11888463. DOI: 10.1101/2025.02.25.640192.

Eosinophilic esophagitis in the "atopic march": dupilumab as an "umbrella" strategy for multiple coexisting atopic diseases.

Lutzu N, Favale A, Demurtas M, Del Giacco S, Onali S, Fantini M Front Med (Lausanne). 2025; 11:1513417.

PMID: 39906352 PMC: 11790572. DOI: 10.3389/fmed.2024.1513417.

Exploring the Impact of Gender on the Characteristics and Complications of Eosinophilic Esophagitis.

Patel H, Elmer J, Liaquat H JGH Open. 2024; 8(12):e70059.

PMID: 39713748 PMC: 11660561. DOI: 10.1002/jgh3.70059.

Eosinophilic esophagitis.

Erdle S, Carr S, Chan E, Robertson K, Watson W Allergy Asthma Clin Immunol. 2024; 20(Suppl 3):72.

PMID: 39702284 PMC: 11660462. DOI: 10.1186/s13223-024-00929-0.

Critical and diverse role of alarmin cytokines in parasitic infections.

Xing Z, Liu S, He X Front Cell Infect Microbiol. 2024; 14:1418500.

PMID: 39559705 PMC: 11570582. DOI: 10.3389/fcimb.2024.1418500.

References

Malerba G, Lauciello M, Scherpbier T, Trabetti E, Galavotti R, Cusin V . Linkage analysis of chromosome 12 markers in Italian families with atopic asthmatic children. Am J Respir Crit Care Med. 2000; 162(4 Pt 1):1587-90. DOI: 10.1164/ajrccm.162.4.9909031. View

Zhu X, Wang M, Crump C, Mishra A . An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice. Am J Physiol Gastrointest Liver Physiol. 2009; 297(3):G550-8. PMC: 2739823. DOI: 10.1152/ajpgi.00148.2009. View

Noel R, Putnam P, Rothenberg M . Eosinophilic esophagitis. N Engl J Med. 2004; 351(9):940-1. DOI: 10.1056/NEJM200408263510924. View

Akei H, Mishra A, Blanchard C, Rothenberg M . Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology. 2005; 129(3):985-94. DOI: 10.1053/j.gastro.2005.06.027. View

Blanchard C, Wang N, Stringer K, Mishra A, Fulkerson P, Abonia J . Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006; 116(2):536-47. PMC: 1359059. DOI: 10.1172/JCI26679. View

Konikoff M, Blanchard C, Kirby C, Buckmeier B, Cohen M, Heubi J . Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006; 4(11):1328-36. DOI: 10.1016/j.cgh.2006.08.013. View

Spergel J, Brown-Whitehorn T, Beausoleil J, Shuker M, Liacouras C . Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol. 2007; 119(2):509-11. DOI: 10.1016/j.jaci.2006.11.016. View

Kato A, Favoreto Jr S, Avila P, Schleimer R . TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells. J Immunol. 2007; 179(2):1080-7. PMC: 2220044. DOI: 10.4049/jimmunol.179.2.1080. View

Furuta G, Liacouras C, Collins M, Gupta S, Justinich C, Putnam P . Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007; 133(4):1342-63. DOI: 10.1053/j.gastro.2007.08.017. View

10.

Blanchard C, Mingler M, Vicario M, Abonia J, Wu Y, Lu T . IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007; 120(6):1292-300. DOI: 10.1016/j.jaci.2007.10.024. View

11.

Collins M, Blanchard C, Abonia J, Kirby C, Akers R, Wang N . Clinical, pathologic, and molecular characterization of familial eosinophilic esophagitis compared with sporadic cases. Clin Gastroenterol Hepatol. 2008; 6(6):621-9. PMC: 2701188. DOI: 10.1016/j.cgh.2008.01.004. View

12.

Challa P . Glaucoma genetics. Int Ophthalmol Clin. 2008; 48(4):73-94. PMC: 2637520. DOI: 10.1097/IIO.0b013e318187e71a. View

13.

Liu Y . TSLP in epithelial cell and dendritic cell cross talk. Adv Immunol. 2009; 101:1-25. PMC: 3645262. DOI: 10.1016/S0065-2776(08)01001-8. View

14.

Gudbjartsson D, Bjornsdottir U, Halapi E, Helgadottir A, Sulem P, Jonsdottir G . Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet. 2009; 41(3):342-7. DOI: 10.1038/ng.323. View

15.

Tantibhaedhyangkul U, Tatevian N, Gilger M, Major A, Davis C . Increased esophageal regulatory T cells and eosinophil characteristics in children with eosinophilic esophagitis and gastroesophageal reflux disease. Ann Clin Lab Sci. 2009; 39(2):99-107. View

16.

Oyoshi M, He R, Kumar L, Yoon J, Geha R . Cellular and molecular mechanisms in atopic dermatitis. Adv Immunol. 2009; 102:135-226. DOI: 10.1016/S0065-2776(09)01203-6. View

17.

Tonozuka Y, Fujio K, Sugiyama T, Nosaka T, Hirai M, Kitamura T . Molecular cloning of a human novel type I cytokine receptor related to delta1/TSLPR. Cytogenet Cell Genet. 2001; 93(1-2):23-5. DOI: 10.1159/000056941. View