Vitamin D Status And Pathway Genes In Five European Autoimmune Addison'S Disease Cohorts

Objective: While vitamin D regulates immune cells, little is known about it in autoimmune Addison's disease (AAD). We investigated the vitamin D status in MD patients from five European populations to assess its deficiency. In addition, we studied two case-control cohorts for vitamin D metabolism and pathway genes.Design: Cross-sectional study.Methods: A total of 1028 patients with AAD from Germany (n = 239), Italy (n = 328), Norway (n = 378), UK (n = 44) and Poland (n = 39) and 679 controls from Germany (n = 301) and Norway (n = 378) were studied for 25(OH)D-3 (primary objective). Secondary objectives (1,25(OH)(2)D-3 and pathway genes) were examined in case-controls from Germany and Norway correlating 25(OH)D-3 and single nucleotide polymorphisms within genes encoding the vitamin D receptor (VDR), 1-alpha-hydroxylase (CYP27B1), 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1) and vitamin D binding protein (GC/DBP).Results: Vitamin D deficiency (25(OH)D-3 10-20 ng/mL) was highly prevalent in AAD patients (34-57%), 5-22% were severely deficient (<10 ng/mL), 28-38% insufficient (20-30 ng/mL) and only 7-14% sufficient (>30 ng/mL). Lower 25(OH)D-3 and 1,25(OH)(2)D-3 levels were observed both in Norwegian and German AAD (P = 0.03/0.003 and P = 1 x 10(5/)< 1 x 10(-7), respectively) the former was associated with CYP2R1 (rs1553006) genotype G. Whereas controls achieved sufficient median 25(OH)D-3 in summers (21.4 to 21.9 ng/mL), AAD patients remained largely deficient (18.0 to 21.2 ng/mL) and synthesize less 1,25(OH)(2)D-3.Conclusion: Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of MD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.