ABSTRACT
The Toll-interleukin 1 receptor superfamily includes the genes interleukin 1 receptor-like 1 (IL1RL1), Toll like receptors (TLRs), myeloid differentiation primary-response 88 (MyD88), and MyD88 adaptor-like (TIRAP). This study describes the interaction between MyD88, TIRAP and IL1RL1 against Helicobacter pylori infection. Cases and controls were genotyped at the polymorphic sites MyD88 rs6853, TIRAP rs8177374 and IL1RL1 rs11123923. The results show that specific combinations of IL1RL1-TIRAP (AA-CT; P: 2,8 × 10-17) and MyD88-TIRAP-IL1RL1 (AA-CT-AA; P: 1,4 × 10-8) - but not MyD88 alone-act synergistically against Helicobacter pylori. Nuclear magnetic resonance (NMR) clearly discriminates cases from controls by highlighting significantly different expression levels of several metabolites (tyrosine, tryptophan, phenylalanine, branched-chain amino acids, short chain fatty acids, glucose, sucrose, urea, etc.). NMR also identifies the following dysregulated metabolic pathways associated to Helicobacter pylori infection: phenylalanine and tyrosine metabolism, pterine biosynthesis, starch and sucrose metabolism, and galactose metabolism. Furthermore, NMR discriminates between the cases heterozygous at the IL1RL1 locus from those homozygous at the same locus. Heterozygous patients are characterized by high levels of lactate, and IL1RL1-both associated with anti-inflammatory activity-and low levels of the pro-inflammatory molecules IL-1ß, TNF-α, COX-2, and IL-6.
Subject(s)
Helicobacter Infections/metabolism , Helicobacter pylori , Interleukin-1 Receptor-Like 1 Protein/metabolism , Membrane Glycoproteins/metabolism , Myeloid Differentiation Factor 88/metabolism , Receptors, Interleukin-1/metabolism , Disease Resistance/genetics , Helicobacter Infections/genetics , Humans , Interleukin-1 Receptor-Like 1 Protein/genetics , Magnetic Resonance Spectroscopy , Membrane Glycoproteins/genetics , Myeloid Differentiation Factor 88/genetics , Real-Time Polymerase Chain Reaction , Receptors, Interleukin-1/geneticsABSTRACT
The genes MyD88 and TIRAP encode the adaptor proteins MyD88 and TIRAP. TIRAP plays the crucial role of activating the MyD88-dependent pathway, which in turn controls the immune response (innate and adaptive) to Helicobacter pylori. We looked for an association of MyD88 and TIRAP with H. pylori infection. Cases and controls were genotyped at the polymorphic sites MyD88 rs6853 and TIRAP rs8177374 by real-time PCR. When the genes were analyzed separately, only TIRAP was associated with infection. When the genes were analyzed concurrently, certain combinations of MyD88 and TIRAP protected the host against H. pylori colonization more efficiently than could be done by TIRAP alone.
Subject(s)
Epistasis, Genetic/immunology , Helicobacter Infections , Helicobacter pylori/immunology , Membrane Glycoproteins , Myeloid Differentiation Factor 88 , Polymorphism, Genetic/immunology , Receptors, Interleukin-1 , Adult , Female , Helicobacter Infections/genetics , Helicobacter Infections/immunology , Humans , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Middle Aged , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/immunology , Receptors, Interleukin-1/genetics , Receptors, Interleukin-1/immunologyABSTRACT
BACKGROUND: Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. AIMS: To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. METHODS: Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. RESULTS: Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02-1.43] and 1.27 [1.05-1.53]), diabetes mellitus (odds ratio, 2.35 [1.68-3.29] and 2.12 [1.47-3.05]), chronic constipation (odds ratio, 1.60 [1.30-1.97] and 1.55 [1.23-1.94]), incomplete purge intake (odds ratio, 2.36 [1.90-2.94] and 2.11 [1.68-2.65]) and a runway time >12h (odds ratio, 3.36 [2.40-4.72] and 2.53 [1.74-3.67]). CONCLUSIONS: We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.
