Peroxiredoxin-2 up-regulation in inflammatory bowel disease: Friend or foe?

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic multi-factorial inflammatory disorders. Accumulating investigations have provided compelling evidence that describe the interplay of a complex genetic landscape and inappropriate inflammatory response to intestinal microbes in disease etiopathogenesis but still pose challenges in diagnostic practices. METHOD: In this study, comparative proteomic analysis was conducted to identify disease specific proteins underlying IBD pathogenetic mechanisms. Total blood proteins of the IBD patients and healthy subjects were analyzed with one-dimensional electrophoresis; differentially expressed bands were excised and subjected to matrix-assisted laser desorption ionization-time of flight mass spectrometry along with nanoflow liquid chromatography electrospray ionization-tandem mass spectrometry analysis. Presence of glycosylation, hydroxylation, and phosphorylation post-translational modifications was further investigated by immunoprecipitation. RESULTS: Peroxiredoxin-2 (PRDX2) and hemoglobin-subunits proteins, which are closely involved in the response to oxidative stress, were identified. PRDX2 was selected for further validation using western blot and reverse transcription-polymerase chain reaction. PRDX2 overexpression was restricted to the protein level within the membrane fraction. Immunoprecipitation identified PRDX2 to be post-translationally glycosylated and phosphorylated. CONCLUSION: Our findings demonstrate the implication of PRDX2 in IBD. Future studies are required to establish its functional role and to determine the clinical utility.

Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients.

Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the association of variant allele carriage with IBD risk. We report that GSTT1 null genotype is significantly associated with the risk of CD (OR: 2.5, CI: 1.2-5, P = 0.013) and UC (OR: 3.5, CI: 1.5-8.5, P = 0.004) and can influence Crohn's disease behavior. The interaction between GSTT1 and GSTM1 genes showed that the combined null genotypes were associated with the risk of UC (OR: 3.1, CI: 1.1-9, P = 0.049). Furthermore, when compared to combined 1236CC/CT genotypes, the 1236TT genotype of MDR1 gene was associated with the risk of UC (OR: 3.7, CI: 1.3-10.7, P = 0.03). Meta-analysis demonstrated significantly higher frequencies of 3435T carriage in IBD patients. Our results show that GSTT1 null and MDR1 polymorphisms could play a role in susceptibility to IBD.