Readressing the role of Toll-like receptor-4 alleles in inflammatory bowel disease: colitis, smoking, and seroreactivity.
BACKGROUND
Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting.


OBJECTIVE
To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers.


METHODS
TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed.


RESULTS
UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001).


CONCLUSIONS
The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.
Department of Gastroenterology, University Hospital of Larissa, University of Thessaly, School of Medicine, 41110, Larissa, Greece. amanwl@yahoo.com
Anastassios C
AC
Manolakis
Andreas N
AN
Kapsoritakis
Anastasia
A
Kapsoritaki
Elisavet K
EK
Tiaka
Konstantinos A
KA
Oikonomou
Vassilis
V
Lotis
Dimitra
D
Vamvakopoulou
Ioanna
I
Davidi
Nikolaos
N
Vamvakopoulos
Spyros P
SP
Potamianos
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D004187:Disaccharides / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008351:Mannans / Q000276:immunology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000276:immunology; D016036:Seroepidemiologic Studies; D012907:Smoking / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D004187:Disaccharides; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008351:Mannans; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C014637:laminaribiose; C014647:mannobiose; C032438:chitobiose; D002097:C-Reactive Protein