Confirmation of association between Multiple Sclerosis and CYP27B1
Résumé
Multiple Sclerosis, MS (OMIM #126200) is a complex inflammatory disease, characterised by lesions in the central nervous system. Both genes and environmental factors influence disease susceptibility. One of the environmental factors that has been implicated in MS and autoimmune disease such as type 1 diabetes is vitamin D deficiency, where patients have lower levels of 25-OHD3 in blood than controls. Previtamin D3 is produced in the skin, and in the liver turned into 25-OHD3. In the kidney, skin and immune cells 25-OHD3 is turned into the bioactive 1,25(OH)2D3 by the enzyme coded by CYP27B1 on chromosome 12q13.1-3. 1,25(OH)2D3 binds to the Vitamin D receptor, expressed in T cells and antigen presenting cells. 1,25(OH)2D3 has a suppressive role on the adaptive immune system, decreasing T cell and dendritic cell maturation, proliferation and differentiation, shifting the balance between Th1 and Th2 cells in favor of Th2 cells, and increasing the suppressive function of Tregs. Rs703842 in the 12q13-14 region was associated to MS in a recent study by the ANZgene consortium. We show associations to three SNPs in this region in our Swedish material (2158 cases, 1759 controls) rs4646536, rs10877012, rs10877015 (p=0.01, 0.01 and 3.5 x 10-3, respectively). We imputed rs703842 and performed a joint analysis with the ANZgene results, reaching a significant association of rs703842 (p = 5.1 x 10-11 odds ratio 0.83 (0.79 - 0.88 95% confidence interval). Because of its close association with 25-OHD3 our results lend further support to the role of vitamin D in MS pathology.
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