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Liu, E. ; Lee, H.S.* ; Aronsson, C.A.* ; Hagopian, W.A.* ; Koletzko, S.* ; Rewers, M.J.* ; Eisenbarth, G.S.* ; Bingley, P.J.* ; Bonifacio, E. ; Simell, V.* ; Agardh, D.* ; TEDDY Study Group (Ziegler, A.-G. ; Beyerlein, A. ; Bonifacio, E. ; Hummel, M. ; Hummel, S. ; Foterek, K. ; Kersting, M. ; Knopff, A. ; Koletzko, S. ; Peplow, C. ; Roth, R. ; Stock, J. ; Strauss, E. ; Warncke, K. ; Winkler, C.)

Risk of pediatric celiac disease according to HLA haplotype and country.

N. Engl. J. Med. 371, 42-49 (2014)
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BACKGROUND: The presence of HLA haplotype DR3-DQ2 or DR4-DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG). METHODS: We studied 6403 children with HLA haplotype DR3-DQ2 or DR4-DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart. The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies. RESULTS: The median follow-up was 60 months (interquartile range, 46 to 77). Celiac disease autoimmunity developed in 786 children (12%). Of the 350 children who underwent biopsy, 291 had confirmed celiac disease; an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies. The risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3-DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3-DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4-DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25). CONCLUSIONS: Children with the HLA haplotype DR3-DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood. The higher risk in Sweden than in other countries highlights the importance of studying environmental factors associated with celiac disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gene Dosage; Children; Susceptibility; Autoimmunity; Antibodies; Childhood; Gluten; Teddy
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 0028-4793
e-ISSN 1533-4406
Quellenangaben Volume: 371, Issue: 1, Pages: 42-49 Article Number: , Supplement: ,
Publisher Massachusetts Medical Society (MMS)
Publishing Place Waltham
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Diabetes and Obesity (IDO)
Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 30201 - Metabolic Health
30502 - Diabetes: Pathophysiology, Prevention and Therapy
90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502100-001
G-502290-001
G-501900-229
PubMed ID 24988556
Scopus ID 84903713927
Erfassungsdatum 2014-07-07