Publication details
RAGE gene variants and disease activity in young and adult patients with Crohn disease
| Authors | |
|---|---|
| Year of publication | 2008 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Inflammatory bowel diseases (IBD) comprise several distinct intestinal pathologies such as ulcerative colitis, Crohn disease (CD), indeterminate colitis and several other rare forms. CD is a chronic inflammatory disease characterized by autoimmune granulomatous process affecting transmurally any part of gastrointestinal tract from the mouth to the anus (though typically originating in terminal ileus) with possible extraintestinal manifestations (such as arthritis, osteoporosis, skin lesions, hepathopathy or eye). Intestinal inflammation in CD is accompanied by massive production of cytokines (TNFa), other pro-inflammatory factors (such as S100 proteins - ligands of Receptor of Advanced Glycation End products, RAGE) and reactive oxygen species (ROS) by immune cells participating in inflammation (monocytes/macrophages and polymorphonuclear leucocytes), disruption of intestinal barrier resulting in increased oxidative damage of neighboring as well as distant tissues and excessive intestinal healing sometimes leading to complications such as stenoses, fistulae or abscesses. Since antioxidant capacity of intestinal tissue is quite limited, assessment of the extent of oxidative damage (incl. that of DNA), repair capacity and other aggravating pro-oxidant factors is of crucial importance for developing more efficient and targeted treatment strategy for CD patients. The aim of the study was to investigate relationship between the extent of oxidative stress and DNA damage/repair, disease severity and genetic variants in the RAGE gene in CD patients. Cross-sectional study comprised a total of 46 subjects with CD (mean age 24.2 +/- 11.4 yrs, 22 men/24 women, median age at CD onset was 14.5 yrs). Mean disease duration was 5.4 =/- 5.5 yrs (range 1 - 24 yrs) and its activity was characterised by Crohn Disease Activity Index (CDAI = median 53, range 10 - 295). Disease complications requiring surgery (abscess, fistula or stenosis) were present in 34 (73.9%) of total subjects. All subjects were on salicylates and/or corticosteroids and/or other immunosuppressive drugs or biologicals (anti-TNFa antibody). All subjects were characterised for markers of inflammation (CRP), oxidative stress (superoxiddismutase, glutathioperoxidase, plasma antioxidant capacity, reduced glutathione, malonddialdehyde), DNA damage (DNAsb) and repair capacity (DNArc) by Comet assay (i.e. single cell gel electrophoresis used for quantification of DNA strand breaks in patients lymphocytes and in modified version for measurement of DNA repair capacity of patients lymphocytes (esp. 8-OH guaninglycosylase, OGG1) upon incubation of HeLa cells with photosensitiser-induced DNA damage (8-oxoguanines) with lymphocyte extracts). DNA repair index (DNARI) was calculated as a ration DNArc/DNAsb. Four SNPs in the RAGE gene (-429T/C, -374T/A, G82S and 2184A/G) were detected by PCR. Relationships between disease activity and parameters of oxidative stress, DNA damage/repair were ascertained by Spearman correlation coefficients. Of nine parameters analyzed, only total plasma antioxidant capacity exhibited significant inverse correlation with CDAI (p<0.05). Interestingly, significant positive correlation existed between duration of CD and DNA repair capacity (p<0.05). RAGE -429T/C variant was marginally significantly associated with GSH levels (p=0.05, Kruskal-Wallis ANOVA). |
| Related projects: |