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; Arato, Andras; Lebl, Jan; Soltesz, Gyula; Danne, Thomas; Battelino, Tadej; Schober, Edit
April 2006
Diabetes Care;Apr2006, Vol. 29 Issue 4, p858
Academic Journal
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 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-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.


Related Articles

  • The role of HLA-DQ8 β57 polymorphism in the anti-gluten T-cell response in coeliac disease. Hovhannisyan, Zaruhi; Weiss, Angela; Martin, Alexandra; Wiesner, Martina; Tollefsen, Stig; Yoshida, Kenji; Ciszewski, Cezary; Curran, Shane A.; Murray, Joseph A.; David, Chella S.; Sollid, Ludvig M.; Koning, Frits; Teyton, Luc; Jabri, Bana // Nature;11/27/2008, Vol. 456 Issue 7221, p534 

    Major histocompatibility complex (MHC) class II alleles HLA-DQ8 and the mouse homologue I-Ag7 lacking a canonical aspartic acid residue at position β57 are associated with coeliac disease and type I diabetes. However, the role of this single polymorphism in disease initiation and progression...

  • Protection of Islet Grafts Through Transforming Growth Factor-β--Induced Tolerogenic Dendritic Cells. Thomas, David C.; Wong, F. Susan; Zaccone, Paola; Green, E. Allison; Wållberg, Maja // Diabetes;Sep2013, Vol. 62 Issue 9, p3132 

    In type 1 diabetes, the insulin-producing -cells are destroyed by the immune system. One way of restoring glucose control is to transplant -cells from a donor. Although this procedure may restore endogenous insulin production, immunosuppressive treatment is needed to prevent the recipient from...

  • Multi-SNP Analysis of MHC Region. Aly, Theresa A.; Eller, Elise; Ide, Akane; Gowan, Katherine; Babu, Sunanda R.; Erlich, Henry A.; Rewers, Marian J.; Eisenbarth, George S.; Fain, Pamela R. // Diabetes;May2006, Vol. 55 Issue 5, p1265 

    Technology has become available to cost-effectively analyze thousands of single nucleotide polymorphisms (SNPs). We recently confirmed by genotyping a small series of class I alleles and microsatellite markers that the extended haplotype HLA-A1-B8-DR3 (8.1 AH) at the major histocompatibility...

  • Association of MHC Class I chain-related A (MIC-A) gene polymorphism with Type I diabetes. Gambelunghe, G.; Ghaderi, M.; Cosentino, A.; Falorni, Ad.; Brunetti, P.; Falorni, Al.; Sanjeevi, C. B. // Diabetologia;Apr2000, Vol. 43 Issue 4, p507 

    Aims/hypothesis. A distinct family of MHC genes has been identified in the class III region and denominated MHC Class I chain-related genes (MIC). The MIC-A gene is located between the TNFA and the HLA-B genes. The aim of our study was to test the association of the polymorphism of the MIC-A...

  • Single nucleotide polymorphisms in MHC2TA, the gene encoding the MHC class II tansactivator (CIITA). Patarroyo, J.C.; Stuve, O.; Piskurich, J.F.; Hauser, S.L.; Oksenberg, J.R.; Zamvil, S.S. // Genes & Immunity;Feb2002, Vol. 3 Issue 1, p34 

    Examines the polymorphisms in the promoter regions of the major histocompatibility complex class II transactivator gene. Single nucleotide polymorphism; Allele frequencies; Presence of splice variant at introns.

  • TGF-beta1 Gene Polymorphism in Association with Diabetic Retinopathy Susceptibility: A Systematic Review and Meta-Analysis. Liu, Lei; Jiao, Jinghua; Wang, Yu; Wu, Jingyang; Huang, Desheng; Teng, Weiping; Chen, Lei // PLoS ONE;Apr2014, Vol. 9 Issue 4, p1 

    Background: Transforming growth factor-beta (TGF-β1) gene has been regarded as an important mechanism in angiogenesis, endothelial cell proliferation, adhesion,and the deposition of extracellular matrix. The TGF-β1 gene may be involved in the development of diabetic retinopathy (DR)...

  • Association of transforming growth factor-beta (TGF-β) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese. Wong, Teresa Yuk Hwa; Poon, Peter; Chow, Kai Ming; Szeto, Cheuk Chun; Cheung, Man Kuen; Li, Philip Kam Tao // Kidney International;May2003, Vol. 63 Issue 5, p1831 

    Association of transforming growth factor-beta (TGF-β) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese. Introduction. Transforming growth factor-β (TGF-β) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since...

  • Relationship between Serum Transforming Growth Factor β1 Concentrations and the Duration of Type 1 Diabetes Mellitus in Children and Adolescents. Zorena, Katarzyna; Raczyńska, Dorota; Wiśniewski, Piotr; Malinowska, Ewa; Myśliwiec, Małgorzata; Raczyńska, Krystyna; Rachoń, Dominik // Mediators of Inflammation;2013, Vol. 2013, p1 

    The aim of this study was to evaluate the relationship between serum transforming growth factor β1 (TGF-β1) concentrations and the duration of type 1 diabetes mellitus (T1DM) in children and adolescents. One hundred and sixteen patients with T1DM and 19 healthy controls were examined....

  • Accelerated Diabetes in Rat Insulin Promoter--Tumor Necrosis Factor-∝ Transgenic Nonobese Diabetic Mice Lacking Major Histocompatibility Class II Molecules. Rajagopalan, Govindarajan; Kudva, Yogish C.; Flavell, Richard A.; David, Chella S. // Diabetes;Feb2003, Vol. 52 Issue 2, p342 

    The major predisposing genetic component in type 1 diabetes maps to the major histocompatibility complex locus in both mice and humans. To verify the HLA class II association with disease pathogenesis, we adopted the transgenic approach. Expression of HLA-DQ8, the molecule showing the strongest...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics