Insulin VNTR I/III genotype is associated with autoantibodies against glutamic acid decarboxylase in newly diagnosed type 1 diabetes.
BACKGROUND
In type 1 diabetes (T1D), the influence of age at diagnosis and of the IDDM1 and IDDM2 genetic susceptibility loci on the profile of beta-cell autoantibodies has been demonstrated. We studied these associations in a group of 92 patients (children, adolescents and adults, aged 2-62 years) with newly diagnosed T1D.


METHODS
The prevalence of the HLA-DQB1*02 and *0302 alleles and of the classes of variable number of tandem repeats (VNTR) of the insulin gene (INS), and of beta-cell autoantibodies (GADA, IA-2A, ICA and IAA) was determined. Statistical analysis was performed using linear and logistic regression models.


RESULTS
The presence of IAA, IA-2A and ICA, but not of GADA, was negatively associated with age at diagnosis. Younger patients were more likely to have multiple autoantibodies. There was a tendency of a higher prevalence of IAA in patients with the HLA-DQB1*02/0302 genotype or with the DQB1*0302 allele compared to patients lacking these markers. As a novel observation, the INS VNTR I/III genotype was significantly associated with the presence of GADA (OR = 4.79; p = 0.018).


CONCLUSIONS
The association between the INS VNTR I/III genotype and GADA may suggest that in patients with T1D lacking the INS VNTR I/I genotype, the effect of other susceptibility factors prevails, which promotes the development of autoimmunity to beta-cell antigens other than insulin.
Rajasalu
T
T
Department of Internal Medicine, University of Tartu, Estonia.
Haller
K
K
Salur
L
L
Kisand
K
K
Tillmann
V
V
Schlosser
M
M
Uibo
R
R
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D007328:Insulin / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*
D001323:Autoantibodies; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007328:Insulin; D005968:Glutamate Decarboxylase