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

医学 维生素D与神经学 内科学 痹症科 维生素D缺乏 次等位基因频率 CYP24A1型 内分泌学 胃肠病学 免疫学 等位基因 骨化三醇受体 等位基因频率 基因 生物 生物化学
作者
Kendra A. Young,Melissa E. Munroe,Joel M. Guthridge,Diane L. Kamen,Timothy B. Niewold,Gary S. Gilkeson,Michael H. Weisman,Mariko Ishimori,Jennifer A. Kelly,Patrick M. Gaffney,Kathy H Sivils,Rufei Lu,Daniel J. Wallace,David R. Karp,John B. Harley,Judith A. James,Jill M. Norris
出处
期刊:Annals of the Rheumatic Diseases [BMJ]
卷期号:76 (1): 153-158 被引量:41
标识
DOI:10.1136/annrheumdis-2016-209157
摘要

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.
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