H. pylori isolates with amino acid sequence polymorphisms as presence of both HtrA-L171 & CagL-Y58/E59 increase the risk of gastric cancer

Abstract Background The cytotoxin-associated gene A (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 C-terminal of CagA protein. 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 of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases. Methods A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software. Results A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, 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 carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004). Conclusions In this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, most H. pylori strains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.

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Diversity of 3’ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

10.21203/rs.3.rs-127429/v2 ◽

2021 ◽

Author(s):

Zhijing Xue ◽

Yuanhai You ◽

Lihua He ◽

Yanan Gong ◽

Lu Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Amino Acid ◽

Chinese Population ◽

Statistical Difference ◽

Variable Region ◽

Repeat Region ◽

Geographical Regions ◽

H Pylori ◽

Epiya Motifs

Abstract Background: The cytotoxin-associated gene A (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 C-terminal of CagA protein. 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 of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases.Methods: A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3’ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software.Results: A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, 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 carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which include AC, ABC, ABCC and ABCCCC subtypes. 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 strains are of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residue 893 and 894 flanking the EPIYA motif had a statistically significant association with gastric cancer.

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A simple electronic tool for assessing amino acid sequence polymorphisms within exon-2 of HLA-DPB1 alleles

Human Immunology ◽

10.1016/j.humimm.2020.06.011 ◽

2020 ◽

Vol 81 (8) ◽

pp. 430-436

Author(s):

H. Clifford Sullivan ◽

Loren Gragert ◽

Geoffrey H. Smith ◽

Kelsi Lindblad ◽

Howard M. Gebel ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Exon 2 ◽

Electronic Tool ◽

Sequence Polymorphisms

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Diversity of 3’ Variable Region of cagA Gene in Helicobacter Pylori Strains Isolated from Chinese Population

10.21203/rs.3.rs-127429/v1 ◽

2020 ◽

Author(s):

zhijing Xue ◽

Yuanhai You ◽

Lihua He ◽

Yanan Gong ◽

Lu Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Amino Acid ◽

Chinese Population ◽

Statistical Difference ◽

Variable Region ◽

Repeat Region ◽

Geographical Regions ◽

H Pylori ◽

Epiya Motifs

Abstract 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.

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Phlebotomus papatasi SP15: mRNA expression variability and amino acid sequence polymorphisms of field populations

Parasites & Vectors ◽

10.1186/s13071-015-0914-2 ◽

2015 ◽

Vol 8 (1) ◽

Cited By ~ 10

Author(s):

Marcelo Ramalho-Ortigão ◽

Iliano V. Coutinho-Abreu ◽

Valdir Q. Balbino ◽

Carlos Alberto S. Figueiredo ◽

Rami Mukbel ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Mrna Expression ◽

Phlebotomus Papatasi ◽

Expression Variability ◽

Sequence Polymorphisms

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Malaria Vaccines Based on thePlasmodium falciparumMerozoite Surface Protein 3—Should We Avoid Amino Acid Sequence Polymorphisms or Embrace Them?

The Journal of Infectious Diseases ◽

10.1086/509813 ◽

2007 ◽

Vol 195 (2) ◽

pp. 171-173 ◽

Cited By ~ 6

Author(s):

Allan Saul

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Surface Protein ◽

Malaria Vaccines ◽

Sequence Polymorphisms

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Genomic differentiation within East Asian Helicobacter pylori

10.1101/2021.06.05.447026 ◽

2021 ◽

Author(s):

Yuanhai You ◽

Kaisa Thorell ◽

Lihua He ◽

Koji Yahara ◽

Yoshio Yamaoka ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Amino Acid ◽

Cancer Incidence ◽

Outer Membrane Proteins ◽

East Asian ◽

Fixation Index ◽

3D Protein Structure ◽

Local Conditions ◽

H Pylori

The East Asian region, including China, Japan and Korea, accounts for half of gastric cancer deaths. However, different areas have contrasting gastric cancer incidence and the population structure of Helicobacter pylori in this ethnically diverse region is yet unknown. We aimed to investigate genomic differences in H. pylori between these areas to identify sequence polymorphisms associated with increased cancer risk. We analysed 381 H. pylori genomes collected from different areas of the three countries using phylogenetic and population genetic tools to characterize population differentiation. The functional consequences of Single Nucleotide Polymorphisms (SNPs) with a highest fixation index (Fst) between subpopulations were examined by mapping amino-acid changes on 3D protein structure, solved or modelled. 329/381 genomes belonged to the previously identified hspEAsia population indicating that import of bacteria from other regions of the world has been uncommon. Seven sub-regional clusters were found within hspEAsia, related to sub-populations with various ethnicities, geographies and gastric cancer risks. Sub-population-specific amino-acid changes were found in multi-drug exporters (hefC), transporters (frpB-4), outer membrane proteins (hopI), and several genes involved in host interaction, such as catalase, involved in H2O2 entrance, and a flagellin site mimicking host glycosylation. Several of the top hits including frpB-4, hefC, alpB/hopB, and hofC. were also differentiated within the Americas, indicating that a handful of genes may be key to local geographic adaptation. H. pylori within East Asia are not homogeneous but have become differentiated geographically at multiple loci that have facilitated adaptation to local conditions and hosts. This has important implications for further evaluation of these changes in relation to the varying gastric cancer incidence between geographical areas in this region.

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