IL-1 RN 2/2 genotype and simultaneous carriage of genotypes IL-1 RN 2/2 and IL-1beta-511 T/T associated with oesophagitis in Helicobacter pylori-negative patients.

BACKGROUND: Interleukin-1 receptor antagonist genotype 2/2 is associated with a prolonged and enhanced inflammatory response. It is suspected of being a risk factor for atrophic gastritis and gastric cancer and for some autoimmune diseases. No specific genetic risk factors for oesophagitis have been identified so far and there are no reports of IL-1 polymorphism in relation to oesophageal disease. METHODS: We studied the IL-1RN, IL-1beta-511 and IL-1beta + 3953 polymorphisms in an unselected series of 142 adult patients scheduled for gastrointestinal endoscopy because of dyspepsia. The control group consisted of university staff and students (n = 179). Helicobacter pylori status was determined by antibody testing and bacterial detection. RESULTS: Endoscopic oesophagitis was noted in 40 patients. The IL-1RN 2/2 genotype was significantly more prevalent in the patients with H. pylori-negative oesophagitis than in the control subjects (27% versus 9%; OR 3.574, CI 1.23-10.35, P = 0.034) or in the dyspeptic patients (27% versus 7%; OR 5.089. CI 1.51-17.11, P = 0.009). IL-1beta-511 T/T genotype tended to be more frequent in the H. pylori-negative patients with oesophagitis than in the control subjects (P = 0.071). The strongest association was between the simultaneous carriage of genotypes IL-1RN 2/2 and IL-1beta -511 T/T and H. pylori-negative oesophagitis. where the combined genotype was more prevalent than in the control subjects (23% versus 6%; OR 4.492, CI 1.40-14.46, P = 0.012) or the dyspeptic patients without oesophagitis (23% versus 3%: OR 9.706. CI 2.12-44.42, P = 0.003). CONCLUSIONS: The results indicate that the IL-1RN 2/2 genotype and the carriage of combined genotypes IL-1RN 2/2 + IL-1beta-511 T/T are associated with H. pylori-negative oesophagitis. This is the first report on the association between IL-1 gene polymorphism and oesophagitis.

EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia.

PURPOSE: Erythropoietic response in 10 healthy nonsmoking volunteers exposed to normobaric hypoxia continuously or intermittently 12 h daily for 7 d was evaluated in a randomized cross-over study. METHODS: An oxygen content of 15.4% corresponding to an altitude of 2500 m was created by adding nitrogen into room air in a flat. Venous blood samples for hemoglobin (Hb), hematocrit (Hct), reticulocytes, serum erythropoietin (S-EPO), red cell 2,3-diphosphoglycerate (2,3-DPG), serum ferritin (S-Ferrit), and serum soluble transferrin receptor (S-TransfR) were drawn at 8:00 a.m. RESULTS: S-EPO was increased from baseline values of 22.9+/-9.6 and 20.5+/-10.1 U x L(-1) to 40.7+/-12.9 (P < 0.05) and 35+/-14.3 U x L(-1) (P < 0.05) after the first night in continuous and intermittent hypoxia, respectively, and remained elevated throughout both exposures. Hb and Hct values did not show any significant changes. Red cell 2,3-DPG rose from baseline a value of 5.0+/-0.8 to 5.9+/-0.7 mmol x L(-1) (P < 0.05) after the first day in continuous hypoxia and from 5.2+/-0.7 mmol x L(-1) to 6.1+/-0.5 mmol x L(-1) on day 3 (P < 0.05) during intermittent hypoxia. The reticulocyte count rose significantly (P < 0.05) after 5 d in both experiments. S-transferrin receptor level rose significantly from 2.2+/-0.4 and 2.1+/-0.5 mg x L(-1) to 2.6+/-0.5 mg x L(-1) and 2.3+/-0.6 mg x L(-1) on day 5 (P < 0.05), to 2.7+/-0.5 mg x L(-1) and 2.5+/-0.6 mg x L(-1) on day 7 (P < 0.05) under continuous and intermittent hypoxia, respectively. CONCLUSIONS: We suggest that intermittent exposure to moderate normobaric hypoxia 12 h daily for 1 wk induces a similar stimulation of erythropoiesis as continuous exposure.