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Protection From Type 1 Diabetes by Vitamin D Receptor Haplotypes
Author(s) -
RAMOSLOPEZ ELIZABETH,
JANSEN THOMAS,
IVASKEVICIUS VYTAUTAS,
KAHLES HEINRICH,
KLEPZIG CHRISTIAN,
OLDENBURG JOHANNES,
BADENHOOP KLAUS
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1375.050
Subject(s) - calcitriol receptor , vitamin d and neurology , haplotype , genotype , medicine , endocrinology , type 2 diabetes , diabetes mellitus , cyp24a1 , polymorphism (computer science) , biology , genetics , gene
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.