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Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease

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Abstract

Beside its traditional role in skeletal health, vitamin D is believed to have multiple immunosuppressant properties, and low vitamin D status has been suggested to be a risk factor in the development of autoimmune disease. We investigated the association between vitamin D status and development of autoimmune disease. We included a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D). We followed the participants by linkage to the Danish National Patient Register (median follow-up time 10.8 years). Relative risks of autoimmune disease were estimated by Cox regression and expressed as hazard ratios, HRs (95 % confidence intervals CIs). There were 525 cases of incident autoimmune disease. The risk for a 10 nmol/l higher vitamin D was: for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98); thyrotoxicosis (HR = 0.83, 95 % CI 0.72, 0.96); type 1 diabetes (HR = 0.95, 95 % CI 0.88, 1.02), multiple sclerosis (HR = 0.89, 95 % CI 0.74, 1.07), iridocyclitis (HR = 1.00, 95 % CI 0.86, 1.17); Crohn’s disease (HR = 0.95, 95 % CI 0.80, 1.13), ulcerative colitis (HR = 0.88, 95 % CI 0.75, 1.04); psoriasis vulgaris (HR = 0.99, 95 % CI 0.86, 1.13); seropositive rheumatoid arthritis (HR = 0.97, 95 % CI 0.89, 1.07), and polymyalgia rheumatica (HR = 0.94, 95 % CI 0.83, 1.06). We found statistically significant inverse associations between vitamin D status and development of any autoimmune disease and thyrotoxicosis in particular. Our findings suggest a possible protective role of a higher vitamin D status on autoimmune disease but warrant further studies to clarify causality.

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References

  1. M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357, 266–281 (2007)

    Article  CAS  PubMed  Google Scholar 

  2. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and cause-specific mortality: a general population study. PLoS One 7, e52423 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population. Cardiology 123, 62–70 (2012)

    Article  CAS  PubMed  Google Scholar 

  4. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, K. Rasmussen et al., Vitamin D status and 5-year changes in urine albumin creatinine ratio and parathyroid hormone in a general population. Endocrine 44, 473–480 (2013)

    Article  CAS  PubMed  Google Scholar 

  5. T. Skaaby, L.L. Husemoen, T. Martinussen, J.P. Thyssen, M. Melgaard, B.H. Thuesen et al., Vitamin D status, filaggrin genotype, and cardiovascular risk factors: a Mendelian randomization approach. PLoS One 8, e57647 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine 43, 618–625 (2013)

    Article  CAS  PubMed  Google Scholar 

  7. T. Skaaby, L.L. Husemoen, A. Borglykke, T. Jorgensen, B.H. Thuesen, C. Pisinger et al., Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine 47, 213–220 (2013)

    Article  PubMed  Google Scholar 

  8. T. Skaaby, L.L. Husemoen, B.H. Thuesen, C. Pisinger, T. Jorgensen, N. Roswall et al., Prospective population-based study of the association between serum 25-hydroxyvitamin-D levels and the incidence of specific types of cancer. Cancer Epidemiol. Biomarkers Prev. 23, 1220–1229 (2014)

    Article  CAS  PubMed  Google Scholar 

  9. T. Skaaby, L.L. Husemoen, B.H. Thuesen, C. Pisinger, T. Jorgensen, R.V. Fenger et al., Vitamin D status and chronic obstructive pulmonary disease: a prospective general population study. PLoS One 9, e90654 (2014)

    Article  PubMed Central  PubMed  Google Scholar 

  10. M. Hewison, An update on vitamin D and human immunity. Clin. Endocrinol. (Oxf) 76, 315–325 (2012)

    Article  CAS  Google Scholar 

  11. A. Latina, D. Gullo, F. Trimarchi, S. Benvenga, Hashimoto’s thyroiditis: similar and dissimilar characteristics in neighboring areas. Possible implications for the epidemiology of thyroid cancer. PLoS One 8, e55450 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Y. Arnson, H. Amital, Y. Shoenfeld, Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann. Rheum. Dis. 66, 1137–1142 (2007)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. P. Pludowski, M.F. Holick, S. Pilz, C.L. Wagner, B.W. Hollis, W.B. Grant et al., Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-A review of recent evidence. Autoimmun. Rev. 12, 976–989 (2013)

    Article  CAS  PubMed  Google Scholar 

  14. P. Szodoray, B. Nakken, J. Gaal, R. Jonsson, A. Szegedi, E. Zold et al., The complex role of vitamin D in autoimmune diseases. Scand. J. Immunol. 68, 261–269 (2008)

    Article  CAS  PubMed  Google Scholar 

  15. K.L. Munger, S.M. Zhang, E. O’Reilly, M.A. Hernan, M.J. Olek, W.C. Willett et al., Vitamin D intake and incidence of multiple sclerosis. Neurology 62, 60–65 (2004)

    Article  CAS  PubMed  Google Scholar 

  16. K.L. Munger, L.I. Levin, B.W. Hollis, N.S. Howard, A. Ascherio, Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296, 2832–2838 (2006)

    Article  CAS  PubMed  Google Scholar 

  17. A. Ascherio, K.L. Munger, R. White, K. Kochert, K.C. Simon, C.H. Polman et al., Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 71, 306–314 (2014)

    Article  PubMed Central  PubMed  Google Scholar 

  18. C. Mathieu, C. Gysemans, A. Giulietti, R. Bouillon, Vitamin D and diabetes. Diabetologia 48, 1247–1257 (2005)

    Article  CAS  PubMed  Google Scholar 

  19. G.G. Song, S.C. Bae, Y.H. Lee, Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Clin. Rheumatol. 31, 1733–1739 (2012)

    Article  PubMed  Google Scholar 

  20. M. Osler, A. Linneberg, C. Glumer, T. Jorgensen, The cohorts at the Research Centre for Prevention and Health, formerly ‘The Glostrup Population Studies’. Int. J. Epidemiol. 40, 602–610 (2011)

    Google Scholar 

  21. C.B. Pedersen, The Danish Civil Registration System. Scand. J. Public Health 39, 22–25 (2011)

    Article  PubMed  Google Scholar 

  22. T.F. Andersen, M. Madsen, J. Jorgensen, L. Mellemkjoer, J.H. Olsen, The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan. Med. Bull. 46, 263–268 (1999)

    CAS  PubMed  Google Scholar 

  23. N.M. Nielsen, T. Westergaard, M. Frisch, K. Rostgaard, J. Wohlfahrt, N. Koch-Henriksen et al., Type 1 diabetes and multiple sclerosis: a Danish population-based cohort study. Arch. Neurol. 63, 1001–1004 (2006)

    Article  PubMed  Google Scholar 

  24. M. Aadahl, S.L. von Huth, C. Pisinger, U.N. Toft, C. Glumer, K. Borch-Johnsen et al., Five-year change in physical activity is associated with changes in cardiovascular disease risk factors: the Inter99 study. Prev. Med. 48, 326–331 (2009)

    Article  CAS  PubMed  Google Scholar 

  25. L. Ambye, S. Rasmussen, M. Fenger, T. Jorgensen, K. Borch-Johnsen, S. Madsbad et al., Studies of the Gly482Ser polymorphism of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) gene in Danish subjects with the metabolic syndrome. Diabetes Res. Clin. Pract. 67, 175–179 (2005)

    Article  CAS  PubMed  Google Scholar 

  26. T. Jorgensen, K. Borch-Johnsen, T.F. Thomsen, H. Ibsen, C. Glumer, C. Pisinger, A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur. J. Cardiovasc. Prev. Rehabil. 10, 377–386 (2003)

    Article  PubMed  Google Scholar 

  27. J.P. Thyssen, A. Linneberg, B.C. Carlsen, J.D. Johansen, K. Engkilde, T. Hansen et al., A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study. BMJ Open 1, e000062 (2011)

    Article  PubMed Central  PubMed  Google Scholar 

  28. G.S. Cooper, B.C. Stroehla, The epidemiology of autoimmune diseases. Autoimmun. Rev. 2, 119–125 (2003)

    Article  PubMed  Google Scholar 

  29. R.L. Rabin, A.I. Levinson, The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature. Clin. Exp. Immunol. 153, 19–30 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. A. Misharin, M. Hewison, C.R. Chen, V. Lagishetty, H.A. Aliesky, Y. Mizutori et al., Vitamin D deficiency modulates Graves’ hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology 150, 1051–1060 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. H. Yamashita, S. Noguchi, K. Takatsu, E. Koike, T. Murakami, S. Watanabe et al., High prevalence of vitamin D deficiency in Japanese female patients with Graves’ disease. Endocr. J. 48, 63–69 (2001)

    Article  CAS  PubMed  Google Scholar 

  32. T. Yasuda, Y. Okamoto, N. Hamada, K. Miyashita, M. Takahara, F. Sakamoto et al., Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine 42, 739–741 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. H. Czernobilsky, S. Scharla, H. Schmidt-Gayk, R. Ziegler, Enhanced suppression of 1,25(OH)2D3 and intact parathyroid hormone in Graves’ disease as compared to toxic nodular goiter. Calcif. Tissue Int. 42, 5–12 (1988)

    Article  CAS  PubMed  Google Scholar 

  34. T. Kawakami-Tani, E. Fukawa, H. Tanaka, Y. Abe, I. Makino, Effect of 1 alpha-hydroxy vitamin D3 on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves’ disease. Metabolism 46, 1184–1188 (1997)

    Article  CAS  PubMed  Google Scholar 

  35. M.A. Pani, K. Regulla, M. Segni, S. Hofmann, M. Hufner, A.M. Pasquino et al., A polymorphism within the vitamin D-binding protein gene is associated with Graves’ disease but not with Hashimoto’s thyroiditis. J. Clin. Endocrinol. Metab. 87, 2564–2567 (2002)

    CAS  PubMed  Google Scholar 

  36. C.E. Jennings, C.J. Owen, V. Wilson, S.H. Pearce, A haplotype of the CYP27B1 promoter is associated with autoimmune Addison’s disease but not with Graves’ disease in a UK population. J. Mol. Endocrinol. 34, 859–863 (2005)

    Article  CAS  PubMed  Google Scholar 

  37. E.R. Lopez, O. Zwermann, M. Segni, G. Meyer, M. Reincke, J. Seissler et al., A promoter polymorphism of the CYP27B1 gene is associated with Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease and type 1 diabetes mellitus in Germans. Eur. J. Endocrinol. 151, 193–197 (2004)

    Article  CAS  PubMed  Google Scholar 

  38. G. Effraimidis, K. Badenhoop, J.G. Tijssen, W.M. Wiersinga, Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur. J. Endocrinol. 167, 43–48 (2012)

    Article  CAS  PubMed  Google Scholar 

  39. P.B. Wilson, Serum 25-hydroxy vitamin D status in individuals with psoriasis in the general population. Endocrine 44, 537–539 (2013)

    Article  CAS  PubMed  Google Scholar 

  40. J.F. Merola, J. Han, T. Li, A.A. Qureshi, No association between vitamin D intake and incident psoriasis among US women. Arch. Dermatol. Res. 306, 305–307 (2014)

    Article  CAS  PubMed  Google Scholar 

  41. P. Gisondi, M. Rossini, C.A. Di, L. Idolazzi, S. Farina, G. Beltrami et al., Vitamin D status in patients with chronic plaque psoriasis. Br. J. Dermatol. 166, 505–510 (2012)

    Article  CAS  PubMed  Google Scholar 

  42. J. Orgaz-Molina, A. Buendia-Eisman, M.A. Arrabal-Polo, J.C. Ruiz, S. Arias-Santiago, Deficiency of serum concentration of 25-hydroxy vitamin D in psoriatic patients: a case-control study. J. Am. Acad. Dermatol. 67, 931–938 (2012)

    Article  CAS  PubMed  Google Scholar 

  43. A.A. Levin, S. Aleissa, N. Dumont, F. Martinez, C. Donovan, S.C. Au et al., A randomized, prospective, sham-controlled study of localized narrow-band UVB phototherapy in the treatment of plaque psoriasis. J. Drugs Dermatol. 13, 922–926 (2014)

    PubMed  Google Scholar 

  44. I. Heier, E. Soyland, A.L. Krogstad, C. Rodriguez-Gallego, M.S. Nenseter, F.L. Jahnsen, Sun exposure rapidly reduces plasmacytoid dendritic cells and inflammatory dermal dendritic cells in psoriatic skin. Br. J. Dermatol. 165, 792–801 (2011)

    Article  CAS  PubMed  Google Scholar 

  45. A. Shah, The pathologic and clinical intersection of atopic and autoimmune disease. Curr. Allergy Asthma Rep. 12, 520–529 (2012)

    Article  CAS  PubMed  Google Scholar 

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Ethics standards

The studies were approved by the Ethics Committee of Copenhagen and the Danish Data Protection Agency, and the recommendations of the Declaration of Helsinki were followed. Participants gave their informed written consent.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Research Centre for Prevention and Health, Glostrup University Hospital, Nordre Ringvej 57, Building 84/85, 2600, Glostrup, Denmark

    Tea Skaaby, Lise Lotte Nystrup Husemoen, Betina Heinsbæk Thuesen & Allan Linneberg

  2. Department of Clinical Experimental Research, Glostrup University Hospital, Nordre Ringvej 57, 2600, Glostrup, Denmark

    Allan Linneberg

  3. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark

    Allan Linneberg

Authors
  1. Tea Skaaby
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  2. Lise Lotte Nystrup Husemoen
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Correspondence to Tea Skaaby.

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Skaaby, T., Husemoen, L.L.N., Thuesen, B.H. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine 50, 231–238 (2015). https://doi.org/10.1007/s12020-015-0547-4

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