Crohn's disease activity versus extent of DNA damage/repair and variability in the RAGE gene

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Authors

PÁCAL Lukáš VARVAŘOVSKÁ Jana SÝKORA Josef KOŽELUHOVÁ Jana RUŠAVÝ Zdeněk RACEK Jaroslav ŠTĚTINA Rudolf KAŇKOVÁ Kateřina

Year of publication 2010
Type Article in Periodical
Magazine / Source Scripta Medica
MU Faculty or unit

Faculty of Medicine

Citation
Field Other specializations of internal medicine
Keywords AGEs; Crohn; glycoxidation; nutrigenetics; RAGE
Description The aim of the study was to investigate relationships between the extent of oxidative stress and DNA damage/repair, disease severity and selected genetic variants in the RAGE gene in Crohns disease (CD) patients. Study comprised a total of 46 subjects with CD and 99 control subjects. Disease activity was characterised by Crohn Disease Activity Index (CDAI) and pediatric CDAI (PCDAI) and complications requiring surgery (abscess, fistula or stenosis). Selected markers of oxidative stress (superoxide dismutase (Ery-SOD), glutathione peroxidise (WB-GPx), total plasma antioxidant capacity (P-tAOC), reduced glutathione (Ery-GSH) and malondialdehyde (P-MDA)), DNA damage (DNA single strand breaks) and repair capacity detected (DNArc) by Comet assay were ascertained. Four SNPs in the RAGE gene were detected by PCR. Significant correlation between CD duration and DNArc was identified in adult patients (r = 0.44, P = 0.039) and adult CD subjects had significantly higher Ery-SOD levels (P = 0.0005). In children, both CDAI and PCDAI significantly correlated with P-tAOC (r = -0.5, P = 0.02 and r = -0.53, P = 0.013, respectively) and also with WB-GPx (r = -0.5, P = 0.03 and r = -0.51, P = 0.018, respectively). Children CD patients also exhibited significant correlation between age and Ery-GSH and P-MDA (r = -0.6, P = 0.005 and r = 0.5, P = 0.02, respectively). Significant differences in Ery-GSH and P-MDA were found between CD patients with and without history of complications (P = 0.05 and P = 0.013, respectively). There was no statistically significant relationship between the carrier state of any of the four RAGE SNPs and ox. stress, DNA damage or DNA repair parameters analysed. In conclusion, intestinal inflammation is reflected in selected circulating markers of oxidative and genotoxic stress.
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