Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus
ObjectiveHigher 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...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.881332/full |
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| author | Lauren A. Vanderlinden Elizabeth A. Bemis Jennifer Seifert Joel M. Guthridge Kendra A. Young Mary Kristen Demoruelle Marie Feser Wade DeJager Susan Macwana Ted R. Mikuls James R. O’Dell Michael H. Weisman Jane Buckner Richard M. Keating Patrick M. Gaffney Jennifer A. Kelly Carl D. Langefeld Carl D. Langefeld Kevin D. Deane Judith A. James Vernon Michael Holers Jill M. Norris |
| author_facet | Lauren A. Vanderlinden Elizabeth A. Bemis Jennifer Seifert Joel M. Guthridge Kendra A. Young Mary Kristen Demoruelle Marie Feser Wade DeJager Susan Macwana Ted R. Mikuls James R. O’Dell Michael H. Weisman Jane Buckner Richard M. Keating Patrick M. Gaffney Jennifer A. Kelly Carl D. Langefeld Carl D. Langefeld Kevin D. Deane Judith A. James Vernon Michael Holers Jill M. Norris |
| author_sort | Lauren A. Vanderlinden |
| collection | DOAJ |
| description | ObjectiveHigher 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.MethodsIn 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).ResultsBoth 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).ConclusionGenes 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. |
| first_indexed | 2024-04-13T21:06:54Z |
| format | Article |
| id | doaj.art-8ead74bae78b4210a2dbb92be12d3596 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T21:06:54Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8ead74bae78b4210a2dbb92be12d35962022-12-22T02:29:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.881332881332Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus ErythematosusLauren A. Vanderlinden0Elizabeth A. Bemis1Jennifer Seifert2Joel M. Guthridge3Kendra A. Young4Mary Kristen Demoruelle5Marie Feser6Wade DeJager7Susan Macwana8Ted R. Mikuls9James R. O’Dell10Michael H. Weisman11Jane Buckner12Richard M. Keating13Patrick M. Gaffney14Jennifer A. Kelly15Carl D. Langefeld16Carl D. Langefeld17Kevin D. Deane18Judith A. James19Vernon Michael Holers20Jill M. Norris21Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSchool of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSchool of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesColorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSchool of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSchool of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesDivision of Rheumatology and Immunology, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, United StatesDivision of Rheumatology and Immunology, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, United StatesDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesCenter for Translational Immunology, Benaroya Research Institute (BRI) at Virginia Mason, Seattle, WA, United StatesDivision of Rheumatology, Scripps Health, La Jolla, CA, United States Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesDepartment of Biostatistics and Data Science, Wake Forest School of Medicine, Winston Salem, NC, United StatesCenter for Precision Medicine, Wake Forest School of Medicine, Winston Salem, NC, United StatesSchool of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesSchool of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesColorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesObjectiveHigher 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.MethodsIn 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).ResultsBoth 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).ConclusionGenes 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.881332/fullvitamin Dautoantibody positive (aAb+)autoantibody negative (aAb-)rheumatoid arthritis (RA)systemic lupus erythematosus (SLE)genetic risk score (GRS) |
| spellingShingle | Lauren A. Vanderlinden Elizabeth A. Bemis Jennifer Seifert Joel M. Guthridge Kendra A. Young Mary Kristen Demoruelle Marie Feser Wade DeJager Susan Macwana Ted R. Mikuls James R. O’Dell Michael H. Weisman Jane Buckner Richard M. Keating Patrick M. Gaffney Jennifer A. Kelly Carl D. Langefeld Carl D. Langefeld Kevin D. Deane Judith A. James Vernon Michael Holers Jill M. Norris Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus Frontiers in Immunology vitamin D autoantibody positive (aAb+) autoantibody negative (aAb-) rheumatoid arthritis (RA) systemic lupus erythematosus (SLE) genetic risk score (GRS) |
| title | Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus |
| title_full | Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus |
| title_fullStr | Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus |
| title_full_unstemmed | Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus |
| title_short | Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus |
| title_sort | relationship between a vitamin d genetic risk score and autoantibodies among first degree relatives of probands with rheumatoid arthritis and systemic lupus erythematosus |
| topic | vitamin D autoantibody positive (aAb+) autoantibody negative (aAb-) rheumatoid arthritis (RA) systemic lupus erythematosus (SLE) genetic risk score (GRS) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.881332/full |
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