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Diversity of 3’ Variable Region of cagA Gene in Helicobacter Pylori Strains Isolated from Chinese Population
Jianzhong Zhang
Chinese Center for Disease Control and Prevention
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7056-8206
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: CagA is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the CagA 3’ variable region. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of CagA 3’ variable region and the amino acid polymorphisms in the EPIYA segments, and their association with gastroduodenal diseases.
Methods: A total of 515 H. pylori isolates from patients in 14 different geographical regions of China were collected and the genomic DNA was extracted. The 3’ variable region of the cagA was amplified by polymerase chain reaction (PCR) and then followed by DNA sequencing, and the amino acid sequences were analyzed with MEGA 7.0 software.
Results: A total of 503 (97.7%) H. pylori isolates were cagA-positive and 1,587 EPIYA motifs were obtained, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B’, B’’ and D’) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains were East Asian type, most of them were ABD subtype (82.1%). Only 22 strains were Western type, including types AC, ABC, ABCC and ABCCCC. The CagA-ABD subtype had statistical difference in different geographic regions (P=0.006). There are seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acid residue 893 and 894 had a statistical difference with gastric cancer (P=0.004).
Conclusions: In this study, 503 CagA sequences was studied and analyzed in depth. In Chinese population, most H. pylori isolates are of the CagA-ABD subtype and its presence was associated with gastroduodenal disease. Amino acid polymorphisms at residue 893 and 894 flanking the EPIYA motif had a statistically significant association with gastric cancer.
Keywords
Helicobacter pylori, cagA, EPIYA, gastroduodenal disease, polymorphism
Jianchang
commented on 30 December, 2020
Interesting results. Just wondering how the deletion of AA 893 and 894 affect the tertiary and quaternary structure of CagA and its' binding to SHP2. Any in vitro or ex vivo experiments with gastric epithelium cells expressing different variants of CagA?
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On 24 Dec, 2020
Reviewer #2 agreed
On 23 Dec, 2020
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This preprint is under consideration at Gut Pathogens. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Diversity of 3’ Variable Region of cagA Gene in Helicobacter Pylori Strains Isolated from Chinese Population
Jianzhong Zhang
Chinese Center for Disease Control and Prevention
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7056-8206
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 16 Dec, 2020
Community comments: 1
Editorial decision: Major revision
On 13 Jan, 2021
Review #2 received
Received 12 Jan, 2021
Review #3 received
Received 05 Jan, 2021
Review #1 received
Received 02 Jan, 2021
Reviewer #3 agreed
On 24 Dec, 2020
Reviewer #2 agreed
On 23 Dec, 2020
Reviewers invited
Invitations sent on 22 Dec, 2020
Reviewer #1 agreed
On 22 Dec, 2020
Editor assigned
On 08 Dec, 2020
Submission checks complete
On 08 Dec, 2020
Editor invited
On 08 Dec, 2020
First submitted
On 07 Dec, 2020
Metrics
Comments: 1
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: CagA is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the CagA 3’ variable region. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of CagA 3’ variable region and the amino acid polymorphisms in the EPIYA segments, and their association with gastroduodenal diseases.
Methods: A total of 515 H. pylori isolates from patients in 14 different geographical regions of China were collected and the genomic DNA was extracted. The 3’ variable region of the cagA was amplified by polymerase chain reaction (PCR) and then followed by DNA sequencing, and the amino acid sequences were analyzed with MEGA 7.0 software.
Results: A total of 503 (97.7%) H. pylori isolates were cagA-positive and 1,587 EPIYA motifs were obtained, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B’, B’’ and D’) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains were East Asian type, most of them were ABD subtype (82.1%). Only 22 strains were Western type, including types AC, ABC, ABCC and ABCCCC. The CagA-ABD subtype had statistical difference in different geographic regions (P=0.006). There are seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acid residue 893 and 894 had a statistical difference with gastric cancer (P=0.004).
Conclusions: In this study, 503 CagA sequences was studied and analyzed in depth. In Chinese population, most H. pylori isolates are of the CagA-ABD subtype and its presence was associated with gastroduodenal disease. Amino acid polymorphisms at residue 893 and 894 flanking the EPIYA motif had a statistically significant association with gastric cancer.
Jianchang
commented on 30 December, 2020
Interesting results. Just wondering how the deletion of AA 893 and 894 affect the tertiary and quaternary structure of CagA and its' binding to SHP2. Any in vitro or ex vivo experiments with gastric epithelium cells expressing different variants of CagA?