Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates.

Autor: Tuan VP; Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam.; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan., Yahara K; Antimicrobial Resistance ResearchCenter, National Institute of Infectious Diseases, Tokyo, Japan., Dung HDQ; Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam., Binh TT; Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam., Huu Tung P; Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam., Tri TD; Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam., Thuan NPM; Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam., Khien VV; Department of GI Endoscopy, 108 Central Hospital, Hanoi, Vietnam., Trang TTH; Department of Molecular Biology, 108 Military Central Hospital, Hanoi, Vietnam., Phuc BH; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan.; Department of Microbiology, Cho Ray Hospital, Ho Chi Minh, Vietnam., Tshibangu-Kabamba E; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan., Matsumoto T; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan., Akada J; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan., Suzuki R; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan., Okimoto T; Department of Gastroenterology, Oita University Faculty of Medicine, Yufu, Oita, Japan., Kodama M; Department of Gastroenterology, Oita University Faculty of Medicine, Yufu, Oita, Japan., Murakami K; Department of Gastroenterology, Oita University Faculty of Medicine, Yufu, Oita, Japan., Yano H; Graduate School of Life Sciences, Tohoku University, Sendai, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.; Institute of Medical Science, University of Tokyo, Tokyo, Japan., Fukuyo M; Department of Molecular Oncology, Chiba University, Chiba, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.; Institute of Medical Science, University of Tokyo, Tokyo, Japan., Takahashi N; Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka City, Tokyo, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.; Institute of Medical Science, University of Tokyo, Tokyo, Japan., Kato M; Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.; Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, Japan., Nishiumi S; Department of Gastroenterology, Graduate School of Medicine, Kobe University, Chuou-ku, Kobe, Hyogo, Japan.; Department of Omics Medicine, Hyogo College of Medicine, Hyogo, Japan., Azuma T; Department of Gastroenterology, Graduate School of Medicine, Kobe University, Chuou-ku, Kobe, Hyogo, Japan., Ogura Y; Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.; Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan., Hayashi T; Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan., Toyoda A; Advanced GenomicsCenter, National Institute of Genetics, Shizuoka, Japan., Kobayashi I; Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka City, Tokyo, Japan.; Research Center for Micro-Nano Technology, Hosei University, Tokyo, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.; Institute of Medical Science, University of Tokyo, Tokyo, Japan., Yamaoka Y; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan.; Department of Medicine, gastroenterology section, Baylor College of Medicine, Houston TX, USA.
Jazyk: angličtina
Zdroj: Microbial genomics [Microb Genom] 2021 Nov; Vol. 7 (11).
DOI: 10.1099/mgen.0.000680
Abstrakt: Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.
Databáze: MEDLINE