PMID- 23042942
OWN - NLM
STAT- MEDLINE
DCOM- 20130131
LR  - 20211021
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 303
IP  - 11
DP  - 2012 Dec 1
TI  - Association of HLA-DQ gene with bowel transit, barrier function, and inflammation 
      in irritable bowel syndrome with diarrhea.
PG  - G1262-9
LID - 10.1152/ajpgi.00294.2012 [doi]
AB  - Patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D) carrying human 
      leukocyte antigen (HLA)-DQ2/8 genotypes benefit from gluten withdrawal. Our 
      objective was to compare gastrointestinal barrier function, mucosal inflammation, 
      and transit in nonceliac IBS-D patients and assess association with HLA-DQ2/8 
      status. In 45 IBS-D patients who were naive to prior exclusion of dietary gluten, 
      we measured small bowel (SB) and colonic mucosal permeability by cumulative 
      urinary lactulose and mannitol excretion (0-2 h for SB and 8-24 h for colon), 
      inflammation on duodenal and rectosigmoid mucosal biopsies (obtained in 28 of 45 
      patients), tight junction (TJ) protein mRNA and protein expression in SB and 
      rectosigmoid mucosa, and gastrointestinal and colonic transit by validated 
      scintigraphy. SB mucosal biopsies were stained with hematoxylin-eosin to assess 
      villi and intraepithelial lymphocytes, and immunohistochemistry was used to 
      assess CD3, CD8, tryptase, and zonula occludens 1 (ZO-1); colonic biopsy 
      intraepithelial lymphocytes were quantitated. Associations of HLA-DQ were 
      assessed using Wilcoxon's rank-sum test. Relative to healthy control data, we 
      observed a significant increase in SB permeability (P < 0.001), a borderline 
      increase in colonic permeability (P = 0.10), and a decrease in TJ mRNA expression 
      in rectosigmoid mucosa in IBS-D. In HLA-DQ2/8-positive patients, ZO-1 protein 
      expression in the rectosigmoid mucosa was reduced compared with that in 
      HLA-DQ2/8-negative patients and colonic transit was slower than in 
      HLA-DQ2/8-negative patients. No other associations with HLA genotype were 
      identified. There is abnormal barrier function (increased SB permeability and 
      reduced mRNA expression of TJ proteins) in IBS-D relative to health that may be, 
      in part, related to immunogenotype, given reduced ZO-1 protein expression in 
      rectosigmoid mucosa in HLA-DQ2/8-positive relative to HLA-DQ2/8-negative 
      patients.
FAU - Vazquez-Roque, Maria I
AU  - Vazquez-Roque MI
AD  - Clinical Enteric Neuroscience Translational and Epidemiological Research, College 
      of Medicine, Mayo Clinic, Charlton 8-110, 200 First St. SW, Rochester, MN 55905, 
      USA.
FAU - Camilleri, Michael
AU  - Camilleri M
FAU - Smyrk, Thomas
AU  - Smyrk T
FAU - Murray, Joseph A
AU  - Murray JA
FAU - O'Neill, Jessica
AU  - O'Neill J
FAU - Carlson, Paula
AU  - Carlson P
FAU - Lamsam, Jesse
AU  - Lamsam J
FAU - Eckert, Deborah
AU  - Eckert D
FAU - Janzow, Denise
AU  - Janzow D
FAU - Burton, Duane
AU  - Burton D
FAU - Ryks, Michael
AU  - Ryks M
FAU - Rhoten, Deborah
AU  - Rhoten D
FAU - Zinsmeister, Alan R
AU  - Zinsmeister AR
LA  - eng
GR  - 1RC1-DK-086182/DK/NIDDK NIH HHS/United States
GR  - R01-DK-092179/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121004
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ2 antigen)
RN  - 0 (HLA-DQ8 antigen)
RN  - 8002-80-0 (Glutens)
SB  - IM
MH  - Colon/diagnostic imaging/physiopathology
MH  - Diarrhea/complications/*physiopathology
MH  - Female
MH  - Gastrointestinal Transit/*immunology
MH  - Glutens/immunology
MH  - HLA-DQ Antigens/genetics/*immunology
MH  - Humans
MH  - Intestinal Mucosa/*physiopathology
MH  - Intestine, Small/physiopathology
MH  - Irritable Bowel Syndrome/complications/*immunology/*physiopathology
MH  - Male
MH  - Permeability
MH  - Prospective Studies
MH  - Radionuclide Imaging
MH  - Tight Junctions/metabolism
PMC - PMC3532460
EDAT- 2012/10/09 06:00
MHDA- 2013/02/01 06:00
PMCR- 2013/12/01
CRDT- 2012/10/09 06:00
PHST- 2012/10/09 06:00 [entrez]
PHST- 2012/10/09 06:00 [pubmed]
PHST- 2013/02/01 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - ajpgi.00294.2012 [pii]
AID - GI-00294-2012 [pii]
AID - 10.1152/ajpgi.00294.2012 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2012 Dec 1;303(11):G1262-9. doi: 
      10.1152/ajpgi.00294.2012. Epub 2012 Oct 4.