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
M. MATĚJKOVÁ-BĚHANOVÁ1, M. VAŇKOVÁ1, M.
HILL1, P. KUČERA2, O. CINEK3,
M. ANDĚL4, B. BENDLOVÁ1
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
Summary
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
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