Vitamin D status and pathway genes in five European autoimmune Addison’s disease cohorts

in European Journal of Endocrinology
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  • 1 M Penna-Martinez, Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany
  • 2 G Meyer, Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
  • 3 A Wolff, Department of Clinical Science and KG Jebsen Center for autoimmune disorders and Department of Medicine, University of Bergen and Haukeland University Hospital, Bergen, Norway
  • 4 B Skinningsrud, Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
  • 5 C Betterle, Department of Medicine (DIMED), University of Padua School of Medicine, Padua, Italy
  • 6 A Falorni, Department of Internal Medicine, University of Perugia, Perugia, Italy
  • 7 W Ollier, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, United Kingdom of Great Britain and Northern Ireland
  • 8 Undlien , Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
  • 9 E Husebye, Department of Clinical Science and KG Jebsen Center for autoimmune disorders and Department of Medicine, University of Bergen and Haukeland University Hospital, Bergen, Norway
  • 10 S Pearce, Translational and Clinical Research Institute, Newcastle University, UK, Newcastle, United Kingdom of Great Britain and Northern Ireland
  • 11 A Mitchell, Translational and Clinical Research Institute, Newcastle University, UK, Newcastle , United Kingdom of Great Britain and Northern Ireland
  • 12 K Badenhoop, Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany

Correspondence: Marissa Penna-Martinez, Email: marissa.penna-martinez@kgu.de
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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 AAD 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)D3 (primary objective). Secondary objectives (1,25(OH)2D3 and pathway genes) were examined in case-controls from Germany and Norway correlating 25(OH)D3 and single nucleotide polymorphisms within genes encoding the vitamin D receptor (VDR), 1-α-hydroxylase (CYP27B1), 25-hydroxylase (CYP2R1); 24-hydroxylase (CYP24A1) and vitamin D binding protein (GC/DBP).

RESULTS

Vitamin D deficiency (25(OH)D3 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)D3 and 1,25(OH)2D3 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)D3 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)2D3.

CONCLUSION

Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of AAD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.

 

     European Society of Endocrinology