Endocrine Abstracts

Type 1 diabetes mellitus (T1D) is an autoimmune disease that results from the destruction of insulin producing β cells, in genetic susceptible individuals. Vitamin D (Vit D) is mostly known for its role in bone and calcium metabolism, however it is also involved in the modulation of the immune response. Serum levels of vitamin D partly depend on diet and sunlight exposure. However, genetic factors are also involved. Patients with T1D have been reported to have a higher prevalence of Vit D deficiency. In addition, the vit D supplementation decreases the risk of developing T1D in humans and prevents the disease in animal models. Single Nucleotide Polymorphisms (SNP’s) located within or near genes that encode crucial enzymes for synthesis (DHCR7-rs12785878), metabolism (CYP2R1-rs2060793) and degradation (CYP24A1-rs6013897) of Vit D have been associated with serum levels of Vit D and with the risk for T1D. However, the results are not consistent for all populations. The aim of this study was to determine the association between these SNP’s, in the Vit D pathway and the genetic susceptibility to T1D in the Portuguese population. We conducted a case-control study to analyse the prevalence of these SNP’s in 320 T1D patients and 486 controls, using PCR-RFLP techniques. Allele and genotype frequencies were compared between patients and controls, as well as diverse clinical parameters. Single locus analysis showed an overrepresentation of the rare allele of the SNP in CYP2R1 gene in patients when compared to controls (OR=1.26; 95%CI: 1.02–1.59; P=0.03). No association was found concerning the other two polymorphisms. Our findings suggest that CYP2R1 polymorphisms may be associated with an increased risk to develop T1D and may contribute to a better understanding of the pathogenesis of T1D and of the role of Vit D in autoimmunity.