Vitamin D binding protein gene polymorphisms and risk of type 1 diabetes mellitus among Egyptians

Abstract

Type 1 diabetes (T1DM) is a multifactorial autoimmune disease in which both genetic predisposition and environmental factors participate in its development. Many cellular and epidemiological studies suggest a role for vitamin D in pathogenesis and prevention of T1DM. Polymorphisms of the genes involved in the metabolism of vitamin D may predispose to T1DM. Vitamin D-binding protein (DBP) is the main systemic transporter of vitamin D and is essential for its cellular endocytosis. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: GAT→GAG substitution replaces aspartic acid by glutamic acid in codon 416; and ACG→AAG substitution in codon 420 leads to an exchange of threonine for lysine. These DBP variants lead to differences in the affinity for vitamin D. Few published studies, about the correlation between these alleles and T1DM, yielded conflicting results. Therefore, we investigated the association of these polymorphisms with T1DM in Egyptian subjects. Unrelated 59 children with T1DM and 65 healthy controls were included in this study. The sequence of DBP exon 11, which contains both examined variants, was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined using Restriction Fragment Length Polymorphism analysis (RFLP). At codon 416 the frequency of Glu/Asp alleles was 64.4/35.6% in T1DM patients and 55.4/44.6% in controls (P >0.05). At codon 420 the frequency of Thr/Lys alleles were 88.1/11.9% and 87.7/12.3% (P >0.05), respectively. Distributions of genotypes at both loci, and the common haplotypes constructed by them, were also very similar in both groups (P >0.05). It could be concluded that the studied DNA polymorphisms in the DBP gene are not associated with T1DM in Egyptian patients.

Key words: Type 1 diabetes Mellitus (T1DM), Vitamin D binding protein (DBP), polymorphism