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Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus
  1. Kendra A Young1,
  2. Melissa E Munroe2,
  3. Joel M Guthridge2,
  4. Diane L Kamen3,
  5. Timothy B Niewold4,
  6. Gary S Gilkeson3,
  7. Michael H Weisman5,
  8. Mariko L Ishimori5,
  9. Jennifer Kelly2,
  10. Patrick M Gaffney2,
  11. Kathy H Sivils2,
  12. Rufei Lu2,6,
  13. Daniel J Wallace5,
  14. David R Karp7,
  15. John B Harley8,9,
  16. Judith A James2,6,
  17. Jill M Norris1
  1. 1Colorado School of Public Health, Aurora, Colorado, USA
  2. 2Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  3. 3Medical University of South Carolina, Charleston, South Carolina, USA
  4. 4Mayo Clinic, Rochester, Minnesota, USA
  5. 5Cedars-Sinai Medical Center, Los Angeles, California, USA
  6. 6Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA
  7. 7University of Texas Southwestern Medical Center, Dallas, Texas, USA
  8. 8Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  9. 9US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA
  1. Correspondence to Dr Jill M Norris, Colorado School of Public Health, 13001 E 17th Place, B119, Aurora, CO 80045, USA; Jill.Norris{at}ucdenver.edu

Abstract

Objective We examined whether measures of vitamin D were associated with transitioning to systemic lupus erythematosus (SLE) in individuals at risk for SLE.

Methods 436 individuals who reported having a relative with SLE but who did not have SLE themselves were evaluated at baseline and again an average of 6.3 (±3.9) years later. Fifty-six individuals transitioned to SLE (≥4 cumulative American College of Rheumatology criteria). 25-Hydroxyvitamin D (25[OH]D) levels were measured by ELISA. Six single-nucleotide polymorphisms in four vitamin D genes were genotyped. Generalised estimating equations, adjusting for correlation within families, were used to test associations between the vitamin D variables and the outcome of transitioning to SLE.

Results Mean baseline 25[OH]D levels (p=0.42) and vitamin D supplementation (p=0.65) were not different between those who did and did not transition to SLE. Vitamin D deficiency (25[OH]D <20 ng/mL) was greater in those who transitioned compared with those who did not transition to SLE (46% vs 33%, p=0.05). The association between 25[OH]D and SLE was modified by CYP24A1 rs4809959, where for each additional minor allele increased 25[OH]D was associated with decreased SLE risk: zero minor alleles (adjusted OR: 1.03, CI 0.98 to 1.09), one minor allele (adjusted OR: 1.01, CI 0.97 to 1.05) and two minor alleles (adjusted OR: 0.91, CI 0.84 to 0.98). Similarly, vitamin D deficiency significantly increased the risk of transitioning to SLE in those with two minor alleles at rs4809959 (adjusted OR: 4.90, CI 1.33 to 18.04).

Conclusions Vitamin D status and CYP24A1 may have a combined role in the transition to SLE in individuals at increased genetic risk for SLE.

  • Systemic Lupus Erythematosus
  • Epidemiology
  • Gene Polymorphism

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Footnotes

  • Handling editor Tore K Kvien

  • Contributors KAY, MEM, JAJ and JMN designed the study. All others participated in data acquisition. KAY and JMN participated in data analysis. All authors assisted with the development of the manuscript and gave final approval for publication. The authors were not paid to write this article by a pharmaceutical company or other agency. MEM, KAY, JMN and JAJ had full access to data for the study; KAY and JMN take responsibility for the integrity of the data and the accuracy of the data analysis. JMN had the final responsibility for the decision to submit for publication.

  • Funding Research reported in this publication was supported by the National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institute of Allergy, Immunology and Infectious Diseases and National Institute of General Medical Sciences under award numbers under award numbers P30 AR053483, P30 GM103510, U54 GM104938, U01 AI101934, U19 AI082714.

  • Competing interests None declared.

  • Ethics approval Experiments were performed in accordance with the Helsinki Declaration and approved by the Institutional Review Boards of the Oklahoma Medical Research Foundation, the Medical University of South Carolina and the University of Colorado Denver.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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