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Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy

Sinnett, Charlotte G.; Letley, Darren P.; Narayana, Geetha L.; Patel, Sapna Rohitbhai; Hussein, Nawfal Rasheed; Zaitoun, Abed M.; Robinson, Karen; Atherton, John C.

Authors

Charlotte G. Sinnett

Darren P. Letley

Geetha L. Narayana

Sapna Rohitbhai Patel

Nawfal Rasheed Hussein

Abed M. Zaitoun

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KAREN ROBINSON karen.robinson@nottingham.ac.uk
Professor in Gastrointestinal Infection and Immunity

John C. Atherton



Abstract

Aims Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin, vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. We now aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well it predicted gastric pathology. Methods Gastric biopsies were donated by 39 H. pylori-infected patients attending for endoscopy at Queen’s Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative polymerase chain reaction. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. Results vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (p

Citation

Sinnett, C. G., Letley, D. P., Narayana, G. L., Patel, S. R., Hussein, N. R., Zaitoun, A. M., …Atherton, J. C. (2016). Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy. Journal of Clinical Pathology, 69(11), 968-973. https://doi.org/10.1136/jclinpath-2016-203641

Journal Article Type Article
Acceptance Date Apr 7, 2016
Online Publication Date May 17, 2016
Publication Date Nov 30, 2016
Deposit Date Apr 20, 2016
Publicly Available Date Mar 29, 2024
Journal Journal of Clinical Pathology
Print ISSN 0021-9746
Electronic ISSN 1472-4146
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 69
Issue 11
Pages 968-973
DOI https://doi.org/10.1136/jclinpath-2016-203641
Keywords Toxin; Microbial; Pathogenic; Helicobacter pylori; Inflammation, Gastric pathology
Public URL https://nottingham-repository.worktribe.com/output/786171
Publisher URL https://jcp.bmj.com/content/69/11/968

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