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Exp Clin Endocrinol Diabetes 2010; 118(4): 245-249
DOI: 10.1055/s-0029-1246213
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Genetic Risk Markers Related to Diabetes-Associated Autoantibodies in Young Patients with Type 1 Diabetes in Berlin, Germany

O. Kordonouri1 , R. Hartmann1 , N. Charpentier1 , M. Knip2 , T. Danne1 , J. Ilonen3
  • 1Diabetes Centre for Children and Adolescents, Children's Hospital auf der Bult, Hannover, Germany
  • 2Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
  • 3Immunogenetics Laboratory, University of Turku, Turku, and Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland
Further Information

Publication History

received 29.07.2009 first decision 19.11.2009

accepted 15.12.2009

Publication Date:
05 February 2010 (online)

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Abstract

Aims: To determine the prevalence of genetic risk markers of type 1 diabetes (T1D) in children diagnosed at a single centre in Germany and to assess their relation to diabetes-associated autoantibodies.

Methods: Blood samples from 243 paediatric patients were genotyped for the high-risk HLA haplotypes DR3-DQ2 (DQA1*05-DQB1*02) and DR4-DQ8 (DRB1*0401/2/4/5-DQB1*0302) and PTPN22 C1858 T polymorphism. The patients (51.4% male) were diagnosed with T1D at a median age of 8.6 y. The T1D-related autoantibodies GADA, IAA and IA-2A were analysed at diagnosis.

Results: 166 patients (68.6%) carried the DR3-DQ2, 114 (47.1%) the DR4-DQ8 haplotype, while 41 (16.9%) patients were negative for both. The PTPN22 CC genotype was detected in 177 (72.8%), CT in 58 (23.9%) and TT in eight (3.3%) patients, respectively. The prevalence of T1D-related autoimmunity was 77.0% for IA-2A, 71.6% for GADA and 43.6% for IAA. There were no differences between patients with and without the 1858 T allele in terms of the frequency, levels or number of autoantibodies, but the former were younger at diagnosis than the latter (p=0.002), IA-2A were positively related to HLA DR4-DQ8 (p=0.004) and inversely associated with HLA DR3-DQ2 (p=0.002). GADA-positive patients were older than those without GADA (p=0.004). In multivariate logistic regression analysis including gender and age as confounding variables, DR4-DQ8 (OR 2.56, 95%CI 1.35–4.86) and DR3-DQ2 (OR 0.36, 95%CI 0.19-0.68) were the only independent predictors of IA-2A positivity.

Conclusion: The prevalence of genetic risk markers in Berlin children with T1D is found to be comparable to other Caucasian T1D populations. The presence of IA-2A at diagnosis is strongly associated with the HLA risk haplotypes, but not with PTPN22 polymorphism.

Key words

HLA - PTPN22 polymorphisms - autoantibodies - diabetes - children - GADA - IA-2A - IAA - age-differences

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Correspondence

O. KordonouriMD 

Diabetes Centre for Children and Adolescents

Children's Hospital auf der Bult

Janusz-Korczak-Allee 12

30173 Hannover

Germany

Phone: +49 511 8115 3340

Fax: +49 511 8115 3334

Email: kordonouri@hka.de

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