Genetic risk markers related to diabetes-associated autoantibodies in young patients with type 1 diabetes in berlin, Germany.
OBJECTIVE
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.


CONCLUSIONS
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.
Diabetes Centre for Children and Adolescents, Children's Hospital auf der Bult, Hannover, Germany. kordonouri@hka.de
O
O
Kordonouri
R
R
Hartmann
N
N
Charpentier
M
M
Knip
T
T
Danne
J
J
Ilonen
D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics* / Q000276:immunology; D012044:Regression Analysis; D018709:Statistics, Nonparametric
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22