Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California.
Gastroenterology Service, Department of Internal Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland.
Clin Gastroenterol Hepatol. 2020 Jul;18(8):1769-1776.e1. doi: 10.1016/j.cgh.2019.09.034. Epub 2019 Oct 4.
BACKGROUND & AIMS: Low serum levels of vitamin D have been associated with Crohn's disease (CD). However, it is unclear whether low vitamin D levels cause CD or CD reduces serum vitamin D.
United States military personnel with CD (n = 240) and randomly selected individuals without CD (controls, n = 240) were matched by age, sex, race, military branch, and geography. We measured 25-hydroxyvitamin D in sera 8-3 years (pre-2) and 3 years to 3 months before diagnosis (pre-1) and 3 months before through 21 months after diagnosis (pre-0). We genotyped VDR and GC vitamin D related polymorphisms. We used conditional logistic regression, including adjustments for smoking, season, enlistment status, and deployment, to estimate relative odds of CD according to vitamin D levels and interactions between genetic factors and levels of vitamin D.
Levels of vitamin D before diagnosis were not associated with CD in pre-2 (P trend = .65) or pre-1 samples (P trend = .84). However, we found an inverse correlation between CD and highest tertile of vitamin D level in post-diagnosis samples (P trend = .01; odds ratio, 0.51; 95% CI, 0.30-0.86). Interactions were not detected between vitamin D levels and VDR or GC polymorphisms. We observed an association between VDR Taq1 polymorphism and CD (independent of vitamin D) (P = .02).
In serum samples from military personnel with CD and matched controls, we found no evidence for an association between CD and vitamin D levels up to 8 years before diagnosis. However, we observed an inverse-association between post-diagnosis vitamin D levels and CD. These findings suggest that low vitamin D does not contribute to development of CD-instead, CD leads to low vitamin D.
维生素 D 血清水平低与克罗恩病(CD)有关。然而,尚不清楚低维生素 D 水平是导致 CD,还是 CD 降低血清维生素 D。
我们对 240 名患有 CD 的美国军事人员(病例组)和随机选择的 240 名无 CD 的个体(对照组)进行了匹配,匹配因素包括年龄、性别、种族、军种和地理位置。我们在诊断前 8-3 年(pre-2)、前 3 年至前 3 个月(pre-1)和诊断前 3 个月至 21 个月(pre-0)时测量血清 25-羟维生素 D。我们对 VDR 和 GC 维生素 D 相关多态性进行了基因分型。我们使用条件逻辑回归,包括调整吸烟、季节、入伍状态和部署情况,根据维生素 D 水平和基因因素与维生素 D 水平之间的相互作用,来估计 CD 的相对比值。
在 pre-2(P 趋势 =.65)或 pre-1 样本(P 趋势 =.84)中,诊断前维生素 D 水平与 CD 无关。然而,我们发现诊断后样本中维生素 D 水平最高三分位与 CD 呈负相关(P 趋势 =.01;比值比,0.51;95%可信区间,0.30-0.86)。未检测到维生素 D 水平与 VDR 或 GC 多态性之间的相互作用。我们观察到 VDR Taq1 多态性与 CD 之间存在关联(独立于维生素 D)(P =.02)。
在患有 CD 的军事人员和匹配对照者的血清样本中,我们在诊断前 8 年内没有发现 CD 与维生素 D 水平之间存在关联的证据。然而,我们观察到诊断后维生素 D 水平与 CD 之间呈负相关。这些发现表明,低维生素 D 不会导致 CD 的发生,而是 CD 导致低维生素 D。