Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2016; 22(13): 3581-3591
Published online Apr 7, 2016. doi: 10.3748/wjg.v22.i13.3581
Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease
Yamilka Abreu-Delgado, Raymond A Isidro, Esther A Torres, Alexandra González, Myrella L Cruz, Angel A Isidro, Carmen I González-Keelan, Priscilla Medero, Caroline B Appleyard
Yamilka Abreu-Delgado, Esther A Torres, Alexandra González, Priscilla Medero, Division of Gastroenterology, Department of Medicine, University of Puerto Rico Medical Sciences Campus-School of Medicine, San Juan, PR 00935, United States
Raymond A Isidro, Myrella L Cruz, Angel A Isidro, Caroline B Appleyard, Department of Basic Sciences, Physiology Division, Ponce Health Sciences University-Medical School and Ponce Research Institute, Ponce, PR 00732, United States
Carmen I González-Keelan, Department of Pathology and Laboratory Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, United States
Author contributions: Abreu-Delgado Y and Isidro RA contributed equally to this work; Abreu-Delgado Y, Isidro RA, Torres EA and Appleyard CB designed the research; Abreu-Delgado Y, Torres EA, González A and Medero P recruited subjects and collected material and clinical data; Isidro RA, Cruz ML, Isidro AA and González-Keelan CI performed the assays and analyzed the tissue samples; Abreu-Delgado Y, Isidro RA and Appleyard CB drafted the manuscript; Torres EA, González A, Cruz ML, Isidro AA, González-Keelan CI and Medero P critically revised manuscript for important intellectual content.
Supported by National Institutes of Health Grants, No. R25GM082406 (to Isidro RA); and U54CA163071 to Appleyard CB; the Office of Research from the Ponce Research Institute at Ponce Health Sciences University; William Townsend Porter Predoctoral Fellowship from the American Physiological Society (to Isidro RA); the PHSU Molecular and Genomics Core Laboratory, RCMI Grant No. RR003050/MD007579; the Puerto Rico Clinical and Translational Research Consortium, National Institutes of Health Grant U54MD007587 (to Abreu Y, Medero P and Torres EA).
Institutional review board statement: The study was reviewed and approved by the University of Puerto Rico Medical Sciences Campus Institutional Review Board (protocol number 1250313).
Informed consent statement: All subjects gave written informed consent prior to study inclusion.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Caroline B Appleyard, PhD, Professor, Department of Basic Sciences, Physiology Division, Ponce Health Sciences University-Medical School and Ponce Research Institute, PO Box 7004, Ponce, PR 00732, United States.
Telephone: +1-787-8402575 Fax: +1-787-8413736
Received: October 24, 2015
Peer-review started: October 26, 2015
First decision: November 13, 2015
Revised: December 5, 2015
Accepted: January 18, 2016
Article in press: January 18, 2016
Published online: April 7, 2016

AIM: To determine serum vitamin D levels and colonic vitamin D receptor (VDR) expression in inflammatory bowel disease (IBD) and non-IBD patients and correlate these with histopathology.

METHODS: Puerto Rican IBD (n = 10) and non-IBD (n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis (active/inactive), and scored for the degree of inflammation present (0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale.

RESULTS: The IBD cohort was significantly younger (40.40 ± 5.27, P < 0.05) than the non-IBD cohort (56.70 ± 1.64) with a higher prevalence of vitamin D deficiency (40% vs 20%, respectively) and insufficiency (70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients (1.95 ± 0.25) than in normal-appearing mucosa from control patients (0.25 ± 0.08, P < 0.01) and from IBD patients (0.65 ± 0.36, P < 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients (r = -0.44, P < 0.05) and from IBD patients with Crohn’s disease (r = -0.69, P < 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients (r = 0.38, P < 0.05) and with patient age (r = 0.54, P < 0.01).

CONCLUSION: Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients.

Keywords: Colitis, Inflammation, Vitamin D, Vitamin D receptor, Inflammatory bowel disease

Core tip: Our study examines for the first time the relationship between serum vitamin D levels, colonic vitamin D receptor (VDR) expression, and histologic disease activity. We show in Puerto Rican patients that colonic VDR expression and inflammation are negatively correlated in endoscopically and histologically diseased colon and that serum vitamin D levels positively correlate with VDR expression in endoscopically and histologically normal colon. These findings contribute to our understanding of the role of vitamin D and VDR in patients with inflammatory bowel disease and could affect the current care of these patients.