Martin Leníček1, Dana Duricová, Ondrej Hradsky, Petra Dušátková, Alena Jirásková, Milan Lukáš, Petr Nachtigal, Libor Vítek. 1. *Department of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; †IBD Clinical and Research Center, ISCARE I.V.F. Lighthouse, Prague, Czech Republic; ‡Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; §Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Prague, Czech Republic; and ‖4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Abstract
BACKGROUND: The oxidative stress is thought to play an important role in Crohn's disease (CD). As serum bilirubin represents the major endogenous antioxidant, this article aimed to evaluate in a clinical study, whether serum bilirubin levels and genes affecting its systemic concentrations are associated with CD. METHODS: This exploratory case-control study was based on pediatric (n = 119) and adult (n = 504) patients with CD and 370 appropriate healthy control subjects. The (GT)n and (TA)n dinucleotide variations in heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) gene promoters were determined by fragment analysis. Serum bilirubin levels were compared in a subset of 90 cases and 229 controls, for whom biochemical data were available. RESULTS: Substantially lower serum bilirubin levels were detected in patients with CD compared with controls (7.4 versus 12.1 μmol/L, P < 10). Serum bilirubin levels were significantly lower in patients with CD within all UGT1A1*28 genotypes (P < 0.05). UGT1A1*28 homozygotes with wild-type NOD2 gene variant exhibited significant delay in CD manifestation (P = 0.004), while the protective effect of UGT1A1*28 homozygosity was lost in those patients with mutated NOD2 gene. No associations between CD risk and individual HMOX1 gene variants were observed. CONCLUSIONS: CD is associated with significantly low serum bilirubin levels, most likely as a result of increased oxidative stress accompanying this inflammatory disease. UGT1A1*28 allele homozygosity, responsible for higher bilirubin levels, seems to be an important modifier of CD manifestation.
BACKGROUND: The oxidative stress is thought to play an important role in Crohn's disease (CD). As serum bilirubin represents the major endogenous antioxidant, this article aimed to evaluate in a clinical study, whether serum bilirubin levels and genes affecting its systemic concentrations are associated with CD. METHODS: This exploratory case-control study was based on pediatric (n = 119) and adult (n = 504) patients with CD and 370 appropriate healthy control subjects. The (GT)n and (TA)n dinucleotide variations in heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) gene promoters were determined by fragment analysis. Serum bilirubin levels were compared in a subset of 90 cases and 229 controls, for whom biochemical data were available. RESULTS: Substantially lower serum bilirubin levels were detected in patients with CD compared with controls (7.4 versus 12.1 μmol/L, P < 10). Serum bilirubin levels were significantly lower in patients with CD within all UGT1A1*28 genotypes (P < 0.05). UGT1A1*28 homozygotes with wild-type NOD2 gene variant exhibited significant delay in CD manifestation (P = 0.004), while the protective effect of UGT1A1*28 homozygosity was lost in those patients with mutated NOD2 gene. No associations between CD risk and individual HMOX1 gene variants were observed. CONCLUSIONS:CD is associated with significantly low serum bilirubin levels, most likely as a result of increased oxidative stress accompanying this inflammatory disease. UGT1A1*28 allele homozygosity, responsible for higher bilirubin levels, seems to be an important modifier of CD manifestation.
Authors: Maria Serena Longhi; Marta Vuerich; Alireza Kalbasi; Jessica E Kenison; Ada Yeste; Eva Csizmadia; Byron Vaughn; Linda Feldbrugge; Shuji Mitsuhashi; Barbara Wegiel; Leo Otterbein; Alan Moss; Francisco J Quintana; Simon C Robson Journal: JCI Insight Date: 2017-05-04
Authors: Kathleen M Schieffer; Shannon M Bruffy; Richard Rauscher; Walter A Koltun; Gregory S Yochum; Carla J Gallagher Journal: PLoS One Date: 2017-06-08 Impact factor: 3.240