Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus

Ann Rheum Dis. 2017 Jan;76(1):153-158. doi: 10.1136/annrheumdis-2016-209157. Epub 2016 Jun 9.

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.

Keywords: Epidemiology; Gene Polymorphism; Systemic Lupus Erythematosus.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Adult
  • Aged
  • Alleles
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Longitudinal Studies
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Calcitriol / genetics
  • Risk Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D-Binding Protein / genetics
  • Vitamin D3 24-Hydroxylase / genetics*

Substances

  • Receptors, Calcitriol
  • Vitamin D-Binding Protein
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human