title: Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk.
abstract: Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Vesa-Matti
authors.initials: VM
authors.lastname: Pohjanen
authors.affiliation: Department of Internal Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Olli-Pekka
authors.initials: OP
authors.lastname: Koivurova
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Huhta
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Helminen
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Mäkinen
authors.affiliation: Department of Medical Microbiology and Immunology, Institute of Diagnostics, University of Oulu, Oulu, Finland; Eastern Finland Laboratory Centre Joint Authority Enterprise (ISLAB), Joensuu, Finland.
authors.forename: Jari M
authors.initials: JM
authors.lastname: Karhukorpi
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Internal Medicine, Pietarsaari City Hospital, Pietarsaari, Finland.
authors.forename: Tapio
authors.initials: T
authors.lastname: Joensuu
authors.affiliation: Oulu City Hospital, Oulu, Finland.
authors.forename: Pentti O
authors.initials: PO
authors.lastname: Koistinen
authors.affiliation: Oulu City Hospital, Oulu, Finland.
authors.forename: Jarno M
authors.initials: JM
authors.lastname: Valtonen
authors.affiliation: Department of Internal Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Seppo E
authors.initials: SE
authors.lastname: Niemelä
authors.affiliation: Department of Medical Microbiology and Immunology, Institute of Diagnostics, University of Oulu, Oulu, Finland.
authors.forename: Riitta A
authors.initials: RA
authors.lastname: Karttunen
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005755:Gastrins / Q000097:blood*; D005756:Gastritis / Q000097:blood / Q000235:genetics / Q000382:microbiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D016481:Helicobacter Infections / Q000097:blood / Q000235:genetics / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D020115:Pepsinogen C / Q000097:blood; D010437:Peptic Ulcer / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D005755:Gastrins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C013550:gastrin 17; D020115:Pepsinogen C; D020116:Pepsinogen A