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

in European Journal of Endocrinology
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  • 1 Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, University Hospital Frankfurt, Goethe-University, Germany
  • 2 Department of Clinical Science and KG Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
  • 3 Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
  • 4 Department of Medicine (DIMED), University of Padua School of Medicine, Padua, Italy
  • 5 Department of Internal Medicine, University of Perugia, Perugia, Italy
  • 6 Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK
  • 7 Department of Medicine, Haukeland University Hospital, Bergen, Norway
  • 8 Translational & Clinical Research Institute, Newcastle University, Newcastle, UK

Correspondence should be addressed to M 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 × 10-5/< 1 × 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.

Supplementary Materials

    • Supplemental figure 1. 25(OH)D3 level depending on the season (summer = S, April-October; winter = W, November-March) in five European autoimmune Addison’s disease cohorts.
    • Supplemental figure 2. Comparison of A: 25(OH)D3 (ng/ml) and B: 1,25(OH)2D3 (pg/ml) between autoimmune Addison’s disease (AAD) and healthy controls (HC) in Norway and Germany cohorts according to sex.
    • Supplemental figure 3. Comparison of A: 25(OH)D3 (ng/ml) and B: 1,25(OH)2D3 (pg/ml) between autoimmune Addison’s disease (AAD) and healthy controls (HC) in Norway and Germany cohorts according to AAD phenotypes (isolated AAD and as part of autoimmune polyendocrine syndrome=APS).
    • Supplemental figure 4. Comparison of 25(OH)D3 level between healthy controls (white) and patients with autoimmune Addison’s disease (grey) within summer
    • Supplemental table 1. SNPs analysed using

 

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