HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sumnik, Z. Articles by Schober, E. Search for Related Content PubMed PubMed Citation Articles by Sumnik, Z. Articles by Schober, E. Social Bookmarking                What's this?

Risk of Celiac Disease in Children With Type 1 Diabetes Is Modified by Positivity for HLA-DQB1*02-DQA1*05 andTNF –308A

¹ Motol University Hospital, the Second Medical School, Charles University, Prague, The Czech Republic
² University Children’s Hospital, Department of Pediatric and Adolescent Endocrinology, Ljubljana, Slovenia
³ Clinic of General Pediatrics, Otto-Heubner-Centrum, Charite, Campus Virchow-Klinikum, Humboldt University, Berlin, Germany
⁴ Department of Pediatrics, University of Pecs, Pecs, Hungary
⁵ First Department of Pediatrics, Semmelweis University, Budapest, Hungary
⁶ Department of Pediatrics, The Third Medical School, Charles University, Prague, The Czech Republic
⁷ Kinderkrankenhaus auf der Bult, Hannover, Germany
⁸ University Children’s Hospital, University of Vienna, Vienna, Austria

Address correspondence and reprint requests to Ondrej Cinek, MD, PhD, Department of Pediatrics, Motol University Hospital, Charles University Prague, V Uvalu 84, CZ-150 06, Prague, The Czech Republic. E-mail: ondrej.cinek{at}lfmotol.cuni.cz

OBJECTIVE—The overlap between genetic susceptibility to celiac disease (CD) and to type 1 diabetes is incomplete; therefore, some genetic polymorphisms may significantly modify the risk of CD in subjects with type 1 diabetes. This study aimed to investigate whether the susceptibility to CD in diabetic children is modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03 and by alleles of single nucleotide polymorphisms within the genes encoding CTLA4, transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-, interferon (IFN)-, interleukin (IL)-1, IL-2, IL-6, and IL-10.

RESEARCH DESIGN AND METHODS—Genotypic data were compared between 130 case subjects (children with type 1 diabetes and CD diagnosed using endomysium antibodies) and 245 control subjects (children with type 1 diabetes only, optimally two per case, matched for center, age at type 1 diabetes onset, and type 1 diabetes duration). The subjects were recruited from 10 major European pediatric diabetes centers performing regular screening for CD. The polymorphisms were determined using PCR with sequence-specific primers, and the risk was assessed by building a step-up conditional logistic regression model using variables that were significantly associated with CD in the univariate analysis.

RESULTS—The best-fitted model showed that risk of CD is increased by presence of HLA-DQB1*02-DQA1*05 (odds ratio 4.5 [95% CI 1.8–11], for homozygosity, and 2.0 [1.1–3.7], for a single dose) and also independently by TNF –308A (1.9 [1.1–3.2], for phenotypic positivity), whereas IL1- –889T showed a weak negative association (0.6 [0.4–0.9]).

CONCLUSIONS—The results indicate that the risk of CD in children with type 1 diabetes is significantly modified both by the presence of HLA-DQB1*02-DQA1*05 and by a variant of another gene within the major histocompatibility complex, the TNF –308A.

Abbreviations: CD, celiac disease • IHWC, 13th International Histocompatibility Workshop and Conference • IL, interleukin • PCR-SSP, PCR with sequence-specific primers • SNP, single nucleotide polymorphism • TNF, tumor necrosis factor

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?