title: HLA-DQ genotype is associated with accelerated small bowel transit in patients with diarrhea-predominant irritable bowel syndrome.
abstract: BACKGROUND
  Colonic transit (CT) is accelerated in 46% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Improvement in IBS-D with gluten withdrawal is associated with human leukocyte antigen (HLA)-DQ2 positivity; the mechanism of improvement is unclear.
  
  
  OBJECTIVE
  To determine if HLA-DQ2-positive or HLA-DQ8-positive patients with IBS-D have faster small bowel (SB) or CT than HLA-DQ2-negative and HLA-DQ8-negative patients.
  
  
  METHODS
  Among 94 patients with IBS-D, who previously provided DNA samples, 64 had undergone validated measurements of CT [geometric center at 24 h (GC24)]; 50 of the patients also had measurement of gastric emptying (GE) and 54 of SB transit (colonic filling at 6 h). HLA-DQ status was determined by tag single nucleotide polymorphism approach. Associations of colonic filling at 6 h and GC24 with HLA-DQ2 and HLA-DQ8 status were assessed using analysis of covariance, adjusting for BMI.
  
  
  RESULTS
  Mean age was 40.8±1.6 years; 98.5% were females. In 60 of the 64 patients, celiac disease was excluded by serology or histology. There were no significant differences in age or BMI among the different HLA-DQ groups. Independently, patients positive for HLA-DQ2 had numerically greater colonic filling at 6 h compared with HLA-DQ2-negative (P=0.065), and those positive for HLA-DQ8 had greater colonic filling at 6 h compared with HLA-DQ8-negative patients (P=0.021). Gastric emptying was not associated with HLA-DQ2 and HLA-DQ8 status. Patients positive for both HLA-DQ2 and HLA-DQ8 had greater colonic filling at 6 h (P=0.013) and numerically higher, but not significant, GC24 (P=0.38) compared with HLA-DQ2-negative and HLA-DQ8-negative patients.
  
  
  CONCLUSIONS
  Patients with IBS-D positive for HLA-DQ8 or for both HLA-DQ2 and HLA-DQ8 have faster SB transit. The mechanism of the accelerated SB transit and the effect of gluten withdrawal on SB function in IBS-D deserve further investigation.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Vazquez-Roque
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Paula
authors.initials: P
authors.lastname: Carlson
authors.forename: Sanna
authors.initials: S
authors.lastname: McKinzie
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Murray
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Brantner
authors.forename: Duane D
authors.initials: DD
authors.lastname: Burton
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000328:Adult; D003106:Colon / Q000503:physiopathology; D003967:Diarrhea / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005746:Gastric Emptying; D005772:Gastrointestinal Transit; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D007421:Intestine, Small / Q000503:physiopathology*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008910:Minnesota; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D005983:Glutens