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Abstract
Objective: Vitamin D has been shown to exert multiple immunomodulatory effects and is known to suppress T-cell activation by binding to the vitamin D receptor (VDR). To determine whether VDR gene polymorphisms are related to the susceptibility to celiac disease, we investigated its implication as a candidate gene in the Basque population. Because celiac disease and type 1 diabetes share common susceptibility loci, we also analyzed families with type 1 diabetes mellitus.
Methods: A total of 37 families with celiac disease and 64 type 1 diabetic families of Basque origin with at least one affected offspring were genotyped for four VDR restriction-site polymorphisms (Fok I, Bsm I, Apa I and Taq I). The AFBAC approach was used to test for association.
Results: Comparison of VDR genotypes of the patients with those of 88 healthy individuals identified “ff” as a risk genotype for celiac disease [p = 0.01; OR = 3.45 (1.12–10.79)]. On the other hand, a significantly higher frequency of haplotype “fBAt” was observed in the type 1 diabetic group [pc = 0.02; OR = 4.4 (1.5–15.3)].
Conclusion: Our findings suggest that polymorphisms within the vitamin D receptor gene are markers of susceptibility to or protection from autoimmune diseases, although, at least in the Basque population, association of VDR variants with celiac disease and type 1 diabetes seems to be heterogeneous.
Acknowledgements
This work was funded by grants RGDM-G03/212 and RCMN-C03/08 from the Instituto de Salud Carlos III of the Spanish Ministry of Health. JRB and GPN are FIS researchers supported by the Spanish Ministry of Health Fellowships no. 99/3076 and 03/0064, respectively.