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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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