Vitamin D-binding protein gene polymorphism association with IA-2 autoantibodies in type 1 diabetes

• Published in: Clinical biochemistry 2005-05, Vol.38 (5), p.415-419
• Main Authors: Ongagna, J.C., Pinget, M., Belcourt, A.
• Format: Article
• Language: English
• Subjects: Adult; Autoantibodies - genetics; Case-Control Studies; Child, Preschool; Codon; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Female; Glutamate Decarboxylase - immunology; Glutamic acid decarboxylase autoantibodies (GAD65); Humans; Isoenzymes - immunology; Male; Middle Aged; PCR; Polymorphism, Restriction Fragment Length; Protein tyrosin phosphatase autoantibodies (IA-2); Restriction mapping; Type 1 diabetes; Vitamin D-binding protein; Vitamin D-Binding Protein - genetics
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2004.12.013

Vitamin D-binding protein (DBP) is the main systemic transporter of 1.25(OH) 2D 3 and is essential for its cellular endocytosis. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: GA T→GA G substitution replaces aspartic acid by glutamic acid in codon 416; and A CG→A AG substitution in codon 420 leads to an exchange of threonine for lysine. These DBP variants lead to differences in the affinity for 1.25(OH) 2D 3. Correlations between DBP alleles and type 1 diabetes have been described in different populations. Therefore, we investigated the polymorphism in codon 416 of the DBP gene for an association with autoimmune markers of type 1 diabetes. The present analysis was a case control study. 110 patients, 68 controls, and 115 first-degree relatives were genotyped for the DBP polymorphism in codon 416. DNA typing of DBP locus was performed by the PCR-restriction fragment length polymorphism method (RFLP). The frequencies of the Asp/Glu and Glu/Glu were significantly increased in diabetic subjects with detectable IA-2 antibodies ( P < 0.01). On the contrary, the DBP Glu-containing genotype was not accompanied by differences in the prevalence of GAD65 antibodies. These finding supports a role of the vitamin D endocrine system in the autoimmune process of type 1 diabetes.