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 ACR criteria). 25-hydroxyvitamin D (25[OH]D) levels were measured by ELISA. Six single nucleotide polymorphisms (SNPs) in four vitamin D genes were genotyped. Generalized 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 to those who did not transition to SLE (46% versus 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: 0 minor alleles (adjusted OR:1.03, CI:0.98,1.09), 1 minor allele (adjusted OR:1.01, CI:0.97,1.05), 2 minor alleles (adjusted OR:0.91, CI:0.84,0.98). 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: 1.33,18.04).
Conclusions
Vitamin D status and CYP24A1 may have a combined role in the transition to SLE in individuals at increased genetic risk for SLE.