Subject(s)
Inflammatory Bowel Diseases , Adolescent , Adult , Aged , Child , Female , Humans , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/therapy , Italy , Male , Middle Aged , Secondary Care Centers , Young AdultABSTRACT
BACKGROUND: Inflammatory bowel disease (IBD) is an epithelial barrier disease that is thought to result from a dysregulated interaction with bacteria in the intestine of genetically predisposed individuals. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in the autosomal recessive disease cystic fibrosis, modulates gut permeability, mucus production, and epithelial interactions with bacteria. The cystic fibrosis DeltaF508 mutation is commonly found in the general population and has been shown to result in a reduced number of CFTR molecules at the surface of epithelial cells. Given the important biological functions of CFTR in the intestine, we tested whether this mutation is of relevance to IBD. METHODS: Using DNA heteroduplex analysis, we investigated the distribution of DeltaF508 heterozygosity in 2568 subjects from three independent cohorts of Italian, Swedish, and Scottish IBD patients and controls. RESULTS: In all three cohorts an association between DeltaF508 and Crohn's disease (CD) was observed. Specifically, DeltaF508 heterozygosity was markedly underrepresented in CD patients from Italy and Sweden (P = 0.021 and 0.027 versus controls, respectively), while stratification for disease location revealed an absence of DeltaF508 carriers among Scottish CD patients with right-sided colitis (P = 0.023 versus all other locations). CONCLUSIONS: DeltaF508 heterozygosity might exert a protective effect in CD.
Subject(s)
Crohn Disease/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Mutation , Adolescent , Adult , Crohn Disease/pathology , Crohn Disease/physiopathology , Cystic Fibrosis Transmembrane Conductance Regulator/physiology , Female , Genetic Carrier Screening , Genetic Predisposition to Disease , Genotype , Humans , Italy , Male , Middle Aged , Phenotype , Scotland , SwedenABSTRACT
BACKGROUND: Duodenal hypersensitivity to acid and decreased duodenal clearance of exogenous acid have been reported in functional dyspepsia (FD). However, the relevance of these abnormalities to spontaneous duodenal acid exposure and dyspeptic symptoms in FD is unknown. AIMS: To determine spontaneous duodenal acid exposure and its relationship with symptoms, duodenal sensitivity to acid, and the effects of a 5-HT(3) receptor antagonist on duodenal responses to acid in FD. METHODS: Eleven FD patients with prominent nausea and 11 healthy controls underwent 24-h ambulatory duodenal pH monitoring with assessment of dyspeptic symptoms. On the next day, duodenal bolus infusions of 5 ml of acid and normal saline were given in a randomized double-blind manner and repeated after ondansetron or a placebo. RESULTS: Nighttime duodenal acid exposure was similar, but FD patients had lower duodenal pH and higher duodenal % time (pH < 4) than controls during the daytime and in the second postprandial 2 h (p < 0.05). Seven patients (64%) with duodenal acid exposure above the normal range had higher severity scores for several dyspeptic symptoms including nausea. However, the symptom severity was poorly or weakly correlated to duodenal pH, and brief duodenal acid infusion did not affect any symptoms. Duodenal responses to exogenous acid were unaffected by 5-HT(3) receptor antagonism. CONCLUSIONS: Spontaneous duodenal acid exposure is increased in a subset of FD patients with prominent nausea, and this is associated with more severe dyspeptic symptoms. However, a direct relationship between duodenal acid exposure and symptom severity is lacking.