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If Lupus in family – 5 times more likely to get Lupus if low vitamin D and poor CYP24A1 – June 2016

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

Ann Rheum Dis. 2016 Jun 9. pii: annrheumdis-2016-209157. doi: 10.1136/annrheumdis-2016-209157. [Epub ahead of print]
Young KA1, Munroe ME2, Guthridge JM2, Kamen DL3, Niewold TB4, Gilkeson GS3, Weisman MH5, Ishimori ML5, Kelly J2, Gaffney PM2, Sivils KH2, Lu R6, Wallace DJ5, Karp DR7, Harley JB8, James JA6, Norris JM1.
1Colorado School of Public Health, Aurora, Colorado, USA.
2Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
3Medical University of South Carolina, Charleston, South Carolina, USA.
4Mayo Clinic, Rochester, Minnesota, USA.
5Cedars-Sinai Medical Center, Los Angeles, California, USA.
6Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
7University of Texas Southwestern Medical Center, Dallas, Texas, USA.
8Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.


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.

PMID: 27283331

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PMCID: PMC5360632 Available free on 2018-01-01

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