Physiol. Res. 53: 187-190, 2004

Polymorphism of INS VNTR is Associated with Glutamic Acid Decarboxylase Antibodies and Postprandial C-Peptide in Patients with Onset of Diabetes after 35 Years of Age


1Institute of Endocrinology, 2Department of Cell and Molecular Immunology, Third Faculty of Medicine, Charles University, 3Second Department of Pediatrics, Second Faculty of Medicine, Charles University and 4Second Department of Internal Medicine, Faculty Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic

Received January 16, 2003
Accepted April 11, 2003

Variability in the number of tandem repeats of the insulin gene (INS VNTR) is probably involved in the genetic regulation of insulin secretion. The aim of this study was to investigate the association of INS VNTR polymorphism with the presence of glutamic acid decarboxylase antibodies (GADA) and C-peptide levels in patients with the onset of diabetes after 35 years of age. We investigated 117 patients, median of age 63 (range 40-83) years, median of diabetes duration 8 (range 1-30) years; 31 GADA-positive and 86 GADA-negative subjects. INS VNTR polymorphism was typed indirectly using – 23HphI (T/A) polymorphism, which is in complete linkage disequilibrium with INS VNTR. The I/I, I/III and III/III genotypes were found in 22 (71 %), 8 (26 %), 1 (3 %) GADA-positive individuals and in 39 (45 %), 35 (41 %), 12 (14 %) GADA-negative individuals, respectively. The Class I allele and the genotype I/I were significantly associated with the presence of GADA (OR=2.72, CI 95 %=1.29-5.73 and OR=2.95, CI 95 %=1.22-7.13). The presence of Class III allele was significantly associated with a higher level of postprandial C-peptide in GADA-positive subjects, even when regarding the duration of diabetes. Our results of INS VNTR polymorphism in patients with the onset of diabetes after 35 years of age confirm the association of Class I INS VNTR with autoimmune diabetes and the protective effect of Class III INS VNTR on the insulin secretion in GADA-positive subjects.

Key words
Polymorphism genetics • Diabetes mellitus • Glutamic acid decarboxylase antibodies • C-peptide • Insulin gene

© 2004 by the Institute of Physiology, Czech Academy of Sciences