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The etiology and pathophysiology of type 1 diabetes remain largely elusive with no established concepts for a causal therapy. Efforts to clarify genetic susceptibility and screening for environmental factors have identified the vitamin D system as a contributory pathway that is potentially correctable. This review aims at compiling all genetic studies addressing the vitamin D system in type 1 diabetes. Herein, association studies with case control cohorts are presented as well as family investigations with transmission tests, meta-analyses and intervention trials. Additionally, rare examples of inborn errors of vitamin D metabolism manifesting with type 1 diabetes and their immune status are discussed. We find a majority of association studies confirming a predisposing role for vitamin D receptor (VDR) polymorphisms and those of the vitamin D metabolism, particularly the CYP27B1 gene encoding the main enzyme for vitamin D activation. Associations, however, are tenuous in relation to the ethnic background of the studied populations. Intervention trials identify the specific requirements of adequate vitamin D doses to achieve vitamin D sufficiency. Preliminary evidence suggests that doses may need to be individualized in order to achieve target effects due to pharmacogenomic variation.

Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition