title: Polymorphisms at Locus 4p14 of Toll-Like Receptors TLR-1 and TLR-10 Confer Susceptibility to Gastric Carcinoma in Helicobacter pylori Infection.
abstract: Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia.
authors.forename: M
authors.initials: M
authors.lastname: Ravishankar Ram
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia.
authors.forename: Khean Lee
authors.initials: KL
authors.lastname: Goh
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia.
authors.forename: Alex Hwong Ruey
authors.initials: AH
authors.lastname: Leow
authors.affiliation: Department of Pathology, BP Diagnostics Center Sdn. Bhd., 30250, Ipoh, Perak, Malaysia.
authors.forename: Bee Hoon
authors.initials: BH
authors.lastname: Poh
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia.
authors.forename: Mun Fai
authors.initials: MF
authors.lastname: Loke
authors.affiliation: Life Science Research Division, Bio-Rad Laboratories Pty. Ltd., Gladesville, New South Wales, 2111, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Harrison
authors.affiliation: Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia.
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia.
authors.forename: Jamuna
authors.initials: J
authors.lastname: Vadivelu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002894:Chromosomes, Human, Pair 4; D016207:Cytokines / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011972:Receptor, Insulin / Q000097:blood; D013274:Stomach Neoplasms / Q000150:complications / Q000235:genetics*; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D051201:Toll-Like Receptor 10 / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; D020738:Leptin; D051194:Toll-Like Receptor 1; D051201:Toll-Like Receptor 10; D011972:Receptor, Insulin