Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Autor:	Vanderlinden LA; Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Bemis EA; School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Seifert J; School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Guthridge JM; Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Young KA; Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Demoruelle MK; School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Feser M; School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., DeJager W; Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Macwana S; Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Mikuls TR; Division of Rheumatology and Immunology, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, United States., O'Dell JR; Division of Rheumatology and Immunology, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, United States., Weisman MH; Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, United States., Buckner J; Center for Translational Immunology, Benaroya Research Institute (BRI) at Virginia Mason, Seattle, WA, United States., Keating RM; Division of Rheumatology, Scripps Health, La Jolla, CA, United States., Gaffney PM; Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Kelly JA; Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Langefeld CD; Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston Salem, NC, United States.; Center for Precision Medicine, Wake Forest School of Medicine, Winston Salem, NC, United States., Deane KD; School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., James JA; Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States., Holers VM; School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Norris JM; Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jun 03; Vol. 13, pp. 881332. Date of Electronic Publication: 2022 Jun 03 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.881332
Abstrakt:	Objective: Higher 25-hydroxyvitamin D (25(OH)D) levels have been associated with reduced risk for autoimmune diseases and are influenced by vitamin D metabolism genes. We estimated genetically-determined vitamin D levels by calculating a genetic risk score (GRS) and investigated whether the vitamin D GRS was associated with the presence of autoantibodies related to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in those at increased risk for developing RA and SLE, respectively. Methods: In this cross-sectional study, we selected autoantibody positive (aAb+) and autoantibody negative (aAb-) individuals from the Studies of the Etiologies of Rheumatoid Arthritis (SERA), a cohort study of first-degree relatives (FDRs) of individuals with RA (189 RA aAb+, 181 RA aAb-), and the Lupus Family Registry and Repository (LFRR), a cohort study of FDRs of individuals with SLE (157 SLE aAb+, 185 SLE aAb-). Five SNPs known to be associated with serum 25(OH)D levels were analyzed individually as well as in a GRS: rs4588 ( GC ), rs12785878 ( NADSYN1 ), rs10741657 ( CYP2R1 ), rs6538691 ( AMDHD1 ), and rs8018720 ( SEC23A ). Results: Both cohorts had similar demographic characteristics, with significantly older and a higher proportion of males in the aAb+ FDRs. The vitamin D GRS was inversely associated with RA aAb+ (OR = 0.85, 95% CI = 0.74-0.99), suggesting a possible protective factor for RA aAb positivity in FDRs of RA probands. The vitamin D GRS was not associated with SLE aAb+ in the LFRR (OR = 1.09, 95% CI = 0.94-1.27). The SEC23A SNP was associated with RA aAb+ in SERA (OR = 0.65, 95% CI = 0.43-0.99); this SNP was not associated with SLE aAb+ in LFRR (OR = 1.41, 95% CI = 0.90 - 2.19). Conclusion: Genes associated with vitamin D levels may play a protective role in the development of RA aAbs in FDRs of RA probands, perhaps through affecting lifelong vitamin D status. The GRS and the SEC23A SNP may be of interest for future investigation in pre-clinical RA. In contrast, these results do not support a similar association in SLE FDRs, suggesting other mechanisms involved in the relationship between vitamin D and SLE aAbs not assessed in this study. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Vanderlinden, Bemis, Seifert, Guthridge, Young, Demoruelle, Feser, DeJager, Macwana, Mikuls, O’Dell, Weisman, Buckner, Keating, Gaffney, Kelly, Langefeld, Deane, James, Holers and Norris.)
Databáze:	MEDLINE
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