Document Detail


HLA-DQ genotype is associated with accelerated small bowel transit in patients with diarrhea-predominant irritable bowel syndrome.
MedLine Citation:
PMID:  21490506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
MATERIALS AND 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.
CONCLUSION: 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:
Maria I Vazquez-Roque; Michael Camilleri; Paula Carlson; Sanna McKinzie; Joseph A Murray; Tricia L Brantner; Duane D Burton; Alan R Zinsmeister
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  European journal of gastroenterology & hepatology     Volume:  23     ISSN:  1473-5687     ISO Abbreviation:  Eur J Gastroenterol Hepatol     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-03     Completed Date:  2011-08-23     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  9000874     Medline TA:  Eur J Gastroenterol Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  481-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Colon / physiopathology
Diarrhea / genetics*,  immunology,  physiopathology
Female
Gastric Emptying
Gastrointestinal Transit*
Genetic Predisposition to Disease
Glutens / immunology
HLA-DQ Antigens / genetics*
Humans
Intestine, Small / physiopathology*
Irritable Bowel Syndrome / complications,  genetics*,  immunology,  physiopathology
Male
Minnesota
Phenotype
Retrospective Studies
Grant Support
ID/Acronym/Agency:
1RC1-DK086182/DK/NIDDK NIH HHS; DK057892/DK/NIDDK NIH HHS; DK71003/DK/NIDDK NIH HHS; R01-DK-67071/DK/NIDDK NIH HHS; RC1 DK086182/DK/NIDDK NIH HHS; RC1 DK086182-02/DK/NIDDK NIH HHS; RR24150/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/HLA-DQ Antigens; 0/HLA-DQ2 antigen; 0/HLA-DQ8 antigen; 8002-80-0/Glutens
Comments/Corrections

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