title: Protection from type 1 diabetes by vitamin D receptor haplotypes.
abstract: Vitamin D has been involved in the modulation of calcium and bone metabolism as well as in the immune system, where it suppresses the proliferation of activated T cells. These effects are exerted via the vitamin D receptor (VDR). Polymorphisms within this gene have been exhaustively studied in diverse autoimmune diseases but with inconsistent results. We previously reported a positive association of polymorphisms within the VDR gene (Apa I, Taq I, Bsm I, and Fok I). In the present article we extended our previous reports to seven additional polymorphisms (rs757343, rs9729, rs2853559, rs1989969, rs3847987, rs2238135, and rs4516035) in a larger set of German simplex type 1 diabetes families. Additionally we correlated serum levels of 25(OH)D(3) and 1,25(OH)(2)D(3) with VDR genotypes and haplotypes. The haplotypes "CG" (Taq I-Apa I), "CGG" (Taq I-Apa I-Tru I), "CGC" (Taq I-Apa I-Fok I), "GCTG" (rs9729-Taq I-Apa I-Tru I), and "CGGC"(Taq I-Apa I, Tru I, Fok I) were less often transmitted, thus negatively associated with type 1 diabetes. Patients who carried the genotype "CC" of the rs3847987 polymorphism had higher median serum levels of 25(OH)D(3). Furthermore, the majority of patients with this genotype possessed normal serum levels of 25(OH)D(3). We conclude that variants of the VDR may confer a genetic protection from type 1 diabetes. Furthermore, normal serum levels of 25(OH)D(3) appear to correlate with a VDR genotype. This supports a role of vitamin D in the immune pathogenesis of type 1 diabetes.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramos-Lopez
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansen
authors.forename: Vytautas
authors.initials: V
authors.lastname: Ivaskevicius
authors.forename: Heinrich
authors.initials: H
authors.lastname: Kahles
authors.forename: Christian
authors.initials: C
authors.lastname: Klepzig
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000517:prevention & control*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; D002117:Calcitriol; D002112:Calcifediol