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

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.