Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus.
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.
Colorado School of Public Health, Aurora, Colorado, USA.
Kendra A
KA
Young
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Melissa E
http://orcid.org/0000-0002-6933-9745
ME
Munroe
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Joel M
JM
Guthridge
Medical University of South Carolina, Charleston, South Carolina, USA.
Diane L
DL
Kamen
Mayo Clinic, Rochester, Minnesota, USA.
Timothy B
http://orcid.org/0000-0003-3532-6660
TB
Niewold
Medical University of South Carolina, Charleston, South Carolina, USA.
Gary S
GS
Gilkeson
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Michael H
MH
Weisman
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Mariko L
ML
Ishimori
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Jennifer
J
Kelly
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Patrick M
PM
Gaffney
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Kathy H
KH
Sivils
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.|Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
Rufei
R
Lu
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Daniel J
DJ
Wallace
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
David R
DR
Karp
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.|US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
John B
JB
Harley
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.|Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
Judith A
JA
James
Colorado School of Public Health, Aurora, Colorado, USA.
Jill M
JM
Norris
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood*; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*
D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human
Epidemiology; Gene Polymorphism; Systemic Lupus Erythematosus