title: Associations between IL-1RA polymorphisms and small intestinal bacterial overgrowth among patients with irritable bowel syndrome from India.
abstract: BACKGROUND
  Low-grade inflammation (controlled by pro and anti-inflammatory molecules), induced by gut microbes in patients with small intestinal bacterial overgrowth (SIBO), may be associated with irritable bowel syndrome (IBS). Polymorphisms of IL-RA gene (anti-inflammatory) was evaluated in IBS and healthy subjects (HS); small intestinal mucosal IL-1α and β levels (pro-inflammatory) in relation to the presence of SIBO were evaluated in a subset of patients.
  
  
  METHODS
  Two hundred and twenty-one IBS patients and 273 age- and gender-matched HS were included. Exactly 209 of 221 patients (Rome III) and 273 HS were genotyped (PCR) for IL-1RA polymorphism. Mucosal IL-1α and β levels (pg/mg of biopsy) were estimated (ELISA) in 82/221 patients with and without SIBO (≥10(5)  CFU/mL upper gut aspirate bacteria).
  
  
  RESULTS
  Genotype 1/1 (IL-1RA over-producer) was less frequent among patients than controls (p = 0.007); genotypes 1/3 (p = 0.012, OR = 3.301, 95% CI = 1.31-8.35) and 2/3 (both under-producers; p = 0.009, OR = 7.703, 95% CI = 1.66-35.82) were commoner among IBS. Fifteen of 82 (18.3%) patients had SIBO. Levels of IL-1α and β were higher among patients with SIBO than without (IL-1α: 35.4 [20.1-66.8] vs 25.5 [4.2-65.3], p < 0.001; IL-1β: 206.8 [133.5-365.9] vs 93.1 [25.5-197.7], p < 0.001) and those with bloating than without (p = 0.012; p = 0.015). IL-1β was higher among patients with Bristol stool type 6 than those with type 1-2 (p = 0.002) and type 3-5 (p = 0.007).
  
  
  CONCLUSIONS
  Polymorphisms 1/1 (IL-1RA over-producer) was infrequent and 1/3 and 2/3 (under-producers) frequent among IBS. Increased IL-1α and β levels were associated with SIBO. Increased IL-1β level was predominantly associated with bloating and loose stools (Bristol type 6).
authors: Department of Gastroenterology, Microbiology and Urology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: D
authors: D
authors: Srivastava
authors: U
authors: U
authors: Ghoshal
authors: R D
authors: RD
authors: Mittal
authors: U C
authors: UC
authors: Ghoshal
mesh_terms: D000328:Adult; D004386:Duodenum / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007194:India; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007421:Intestine, Small / Q000382:microbiology*; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta
keywords: functional bowel disease; gut flora; gut inflammation; interleukin; pro-inflammatory cytokine