The cytochrome P450, subfamily XXVIIB, polypeptide 1 gene (CYP27B1) encodes 25-hydroxy-vitamin D3-1-a-hydroxylase, which is expressed in the renal proximal tubule and catalyzes metabolic activation of 25-hydroxyvitamin D3 into 1a, 25-dihydroxyvitamin D3 [1-a,25-(OH)2 D3], the active form of vitamin D (118). As a key enzyme in vitamin D metabolism, mutations of this gene have been shown to cause type 1 vitamin D-dependent rickets (119-122). Two polymorphisms, a promoter region SNP rs10877012 and an intronic SNP rs4646536, were reported to be associated with DM1 by a study of 187 DM1 German families (123). Recently, the DM1 association was confirmed by a large-scale study (124). Besides DM1, Lopez et al. showed also that the CYP27B1 promoter SNP is also associated with Addison's disease, Hashimoto's thyroiditis and Graves' disease (125). The role of vitamin D goes beyond calcium regulation, and there is increasing evidence that it is also involved in regulation of the immune system (126). There is no evidence for association between the vitamin D receptor gene (VDR) polymorphisms and DM1 (127).
DM1 predisposition from vitamin D deficiency and an effect of vitamin D treatment in DM1 prevention have been suggested (128, 129). As a key gene in vitamin D metabolism, the DM1 association of the CYP27B1 gene variation provides new evidence for the role of vitamin D in DM1. This finding has also potential pharmacogenetic value. As the variants are involved in the production of active form of vitamin D, they could serve as the markers for the clinical administration of vitamin D drugs.
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