Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A

Zdenek Sumnik, Ondrej Cinek, Nina Bratanic, Olga Kordonouri, Michal Kulich, Barnabas Roszai, A. Arató, Jan Lebl, G. Soltész, Thomas Danne, Tadej Battelino, Edit Schober

Research output: Contribution to journalArticle

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Abstract

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)-β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, 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 HLADQB1* 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-α -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.

Original languageEnglish
Pages (from-to)858-863
Number of pages6
JournalDiabetes Care
Volume29
Issue number4
Publication statusPublished - 2006

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Celiac Disease
Type 1 Diabetes Mellitus
Tumor Necrosis Factor-alpha
Logistic Models
HLA-DQB1 antigen
Transforming Growth Factors
Genetic Polymorphisms
Genetic Predisposition to Disease
Major Histocompatibility Complex
Interleukin-1
Interleukin-10
Interferons
Genes
Interleukin-2
Single Nucleotide Polymorphism
Interleukin-6
Research Design
Alleles
Odds Ratio
Pediatrics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Sumnik, Z., Cinek, O., Bratanic, N., Kordonouri, O., Kulich, M., Roszai, B., ... Schober, E. (2006). Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A. Diabetes Care, 29(4), 858-863.

Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A. / Sumnik, Zdenek; Cinek, Ondrej; Bratanic, Nina; Kordonouri, Olga; Kulich, Michal; Roszai, Barnabas; Arató, A.; Lebl, Jan; Soltész, G.; Danne, Thomas; Battelino, Tadej; Schober, Edit.

In: Diabetes Care, Vol. 29, No. 4, 2006, p. 858-863.

Research output: Contribution to journalArticle

Sumnik, Z, Cinek, O, Bratanic, N, Kordonouri, O, Kulich, M, Roszai, B, Arató, A, Lebl, J, Soltész, G, Danne, T, Battelino, T & Schober, E 2006, 'Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A', Diabetes Care, vol. 29, no. 4, pp. 858-863.
Sumnik Z, Cinek O, Bratanic N, Kordonouri O, Kulich M, Roszai B et al. Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A. Diabetes Care. 2006;29(4):858-863.
Sumnik, Zdenek ; Cinek, Ondrej ; Bratanic, Nina ; Kordonouri, Olga ; Kulich, Michal ; Roszai, Barnabas ; Arató, A. ; Lebl, Jan ; Soltész, G. ; Danne, Thomas ; Battelino, Tadej ; Schober, Edit. / Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A. In: Diabetes Care. 2006 ; Vol. 29, No. 4. pp. 858-863.
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T1 - Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A

AU - Sumnik, Zdenek

AU - Cinek, Ondrej

AU - Bratanic, Nina

AU - Kordonouri, Olga

AU - Kulich, Michal

AU - Roszai, Barnabas

AU - Arató, A.

AU - Lebl, Jan

AU - Soltész, G.

AU - Danne, Thomas

AU - Battelino, Tadej

AU - Schober, Edit

PY - 2006

Y1 - 2006

N2 - 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)-β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, 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 HLADQB1* 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-α -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.

AB - 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)-β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, 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 HLADQB1* 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-α -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.

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