Diversity of 3’ Variable Region of cagA Gene in Helicobacter Pylori Strains Isolated from Chinese Population
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.
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?
Posted 16 Dec, 2020
On 13 Jan, 2021
Received 12 Jan, 2021
Received 05 Jan, 2021
Received 02 Jan, 2021
On 24 Dec, 2020
On 23 Dec, 2020
Invitations sent on 22 Dec, 2020
On 22 Dec, 2020
On 08 Dec, 2020
On 08 Dec, 2020
On 08 Dec, 2020
On 07 Dec, 2020
Diversity of 3’ Variable Region of cagA Gene in Helicobacter Pylori Strains Isolated from Chinese Population
Posted 16 Dec, 2020
On 13 Jan, 2021
Received 12 Jan, 2021
Received 05 Jan, 2021
Received 02 Jan, 2021
On 24 Dec, 2020
On 23 Dec, 2020
Invitations sent on 22 Dec, 2020
On 22 Dec, 2020
On 08 Dec, 2020
On 08 Dec, 2020
On 08 Dec, 2020
On 07 Dec, 2020
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.
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?