Investigating the Role of Vitamin D in the Transition to Systemic Lupus Erythematosus in Individuals at Risk for the Disease

Kendra A. Young¹, Melissa E. Munroe², Joel M. Guthridge², Diane L. Kamen³, Timothy B. Niewold⁴, Gary S. Gilkeson⁵, Michael H. Weisman⁶, Mariko L. Ishimori⁶, Daniel J Wallace⁷, David R. Karp⁸, John B. Harley⁹, Judith A. James¹⁰ and Jill M. Norris¹¹, ¹Epidemiology, University of Colorado Denver, Aurora, CO, ²Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ³Medicine, Medical University of South Carolina, Charleston, SC, ⁴Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN, ⁵Department of Rheumatology, Medical University of South Carolina, Charleston, SC, ⁶Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, ⁷Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, ⁸Internal Medicine - Rheumatic Diseases, University of Texas Southwestern Medical Center, Dallas, TX, ⁹Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ¹⁰Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ¹¹University of Colorado Denver, Aurora, CO

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Lupus, Vitamin D and family studies

Session Information

Date: Sunday, November 8, 2015

Title: Epidemiology and Public Health Poster I: Comorbidities and Outcomes of Systemic Inflammatory Diseases

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Lower vitamin D levels are associated with increased disease activity in systemic lupus erythematosus (SLE) and individuals with SLE have increased prevalence of vitamin D deficiency. However, there have been no prospective studies on whether vitamin D is associated with transitioning to clinical SLE. We examined whether vitamin D supplement use, 25-hydroxyvitamin D (25[OH]D) levels and single nucleotide polymorphisms (SNPs) in vitamin D genes were associated with transitioning to SLE in individuals at risk for the disease.

Methods: 436 individuals who reported having a relative with SLE but who did not have SLE themselves at baseline were followed-up an average of 6.3 (± 3.9) years later. At both visits, detailed demographic, environmental, clinical, and therapeutic information was collected by questionnaire, and a blood sample was obtained. The 56 individuals (77% ANA positive, 77% European American (EA), 88% female) who transitioned to SLE (> 4 cumulative ACR criteria) were verified by medical record review. 25[OH]D levels were measured by ELISA. Vitamin D deficiency was defined as 25[OH]D <20 ng/ml. Twelve SNPs in 7 vitamin D genes were typed by Immunochip. Ancestry was determined by principal components analysis of the full Immunochip data. Generalized estimating equations (GEE), adjusting for correlation within families, were used to test associations between the vitamin D variables and the categorical outcome of transitioning to SLE. GEE analyses examining the association between SNPs in an additive model and transitioning to SLE was limited to 294 EA, adjusting for age, sex and ancestry.

Results: Mean baseline 25[OH]D levels were not different between those who transitioned to SLE and those who did not transition to SLE (23.0 versus 24.1 ng/ml, p=0.42), nor was vitamin D supplement use (10.7% versus 12.9%, p=0.65). Adjusting for age, sex, race and season of blood draw, transitioning to SLE was not associated with baseline 25[OH]D levels (adjusted OR=0.98, 95% CI 0.95-1.02), being vitamin D deficient (adjusted OR=1.92. 95% CI 0.64-5.77), nor taking vitamin D supplements at baseline (adjusted OR=0.70, 95% CI 0.28-1.79). SNPs in CYP27A1, GC, DHCR7/NADSYN1, CYP2R1, VDR, CYP27B1 and CYP24A1 were also not associated with transitioning to SLE. However, significant effect modification (interaction p-value=0.02) indicated that in those not taking vitamin D supplements, each additional minor allele in rs12794714 in CYP2R1was associated with a decreased risk of transitioning to SLE (adjusted OR= 0.71, 95% CI 0.40-1.25); in those taking supplements, each additional allele resulted in increased risk of transitioning to SLE (adjusted OR= 5.76, 95% CI 0.73-45.75).

Conclusion: 25[OH]D levels at baseline were not associated with transitioning to SLE at follow-up. However, the large effect size of vitamin D deficiency and the interaction between supplement use and CYP2R1 on SLE risk suggests that vitamin D may play a role that is not adequately marked by 25[OH]D levels. To our knowledge, this is the first prospective study examining the association between vitamin D and SLE disease onset, and indicates that vitamin D does not play a strong role in transitioning to SLE.

Disclosure: K. A. Young, None; M. E. Munroe, None; J. M. Guthridge, None; D. L. Kamen, None; T. B. Niewold, None; G. S. Gilkeson, None; M. H. Weisman, None; M. L. Ishimori, None; D. J. Wallace, None; D. R. Karp, None; J. B. Harley, None; J. A. James, None; J. M. Norris, None.

To cite this abstract in AMA style:

Young KA, Munroe ME, Guthridge JM, Kamen DL, Niewold TB, Gilkeson GS, Weisman MH, Ishimori ML, Wallace DJ, Karp DR, Harley JB, James JA, Norris JM. Investigating the Role of Vitamin D in the Transition to Systemic Lupus Erythematosus in Individuals at Risk for the Disease [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/investigating-the-role-of-vitamin-d-in-the-transition-to-systemic-lupus-erythematosus-in-individuals-at-risk-for-the-disease/. Accessed .

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