Tóm tắt
Background: H. pylori CagA protein plays the most critical pathogenesis role of gastroduodenal diseases. CagA translocation is dependent on the CagL protein encoded by the cagL gene. Objectives: This study aimed to investigate CagL amino acid sequence polymorphisms of H. pylori and its associations with gastroduodenal diseases. Materials and methods: The cagL partial nucleotide sequences of 72 H. pylori strains from Vietnamese patients with gastroduodenal disorders were investigated via Sanger sequencing, then were translated into amino acid sequences. Results: The findings showed nine variants of amino acid polymorphism within the CagL hypervariable motif at residues 58–62, in which the DEIGK variant was the most prevalent, accounting for 40.28%, the DKIGK variants represented 30.56%, both DKMGE and DTTGE variants accounted for 8.33%. The five remaining variants, including YEIGK, NEIGQ, NKIGQ, DEIGQ and DTIGK, had low frequencies (1.39–4.17%). Notably, we observed a novel amino acid sequence polymorphism pattern at residues 140-144 with four variants as EAELQ, EGKLK, LGKLK, and EAKLQ, which accounted for 61.11%, 30.56%, 5.56%, and 2.78%, respectively. Stratifying gastroduodenal diseases, the EAELQ variant rates in the gastric cancer and precancerous lesions groups were 86.67% and 70%, respectively, whereas those in the non-atrophic gastritis and peptic ulcers groups were only 47.37% and 44.44%, respectively. The difference in these rates was statistically significant (p=0.038). Conclusion: This preliminary study highlighted the genetic diversity of the H. pylori cagL gene, revealing distinct polymorphism patterns unique to Vietnam. The EAELQ variant at CagL residues 140–144 may serve as an indicator of gastric cancer risk.
| Đã xuất bản | 30-04-2026 | |
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| Số tạp chí | Tập 16 Số 02 (2026) | |
| Phân mục | Nghiên cứu | |
| DOI | 10.34071/jmp.2026.2.953 | |
| Từ khóa | gastric cancer, cagL gene, Helicobacter pylori, amino acid polymorphism, gastroduodenal diseases |
công trình này được cấp phép theo Creative Commons Attribution-phi thương mại-NoDerivatives 4.0 License International .
Bản quyền (c) 2026 Tạp chí Y Dược Huế
Kao CY, Sheu BS, Wu JJ. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis. Biomed J. 2016;39(1):14-23. doi:10.1016/j.bj.2015.06.002
Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153(2):420-429. doi:10.1053/j.gastro.2017.04.022
IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 60.; 1994.
Ogorodnik E, Raffaniello RD. Analysis of the 3’-variable region of the cagA gene from Helicobacter pylori strains infecting patients at New York City hospitals. Microb Pathog. 2013;56:29-34. doi:10.1016/j.micpath.2012.10.003
Cover TL, Lacy DB, Ohi MD. The Helicobacter pylori Cag Type IV Secretion System. Trends Microbiol. 2020;28(8):682-695. doi:10.1016/j.tim.2020.02.004
Plummer M, van Doorn LJ, Franceschi S, Kleter B, Canzian F, Vivas J, et al. Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions. J Natl Cancer Inst. 2007;99(17):1328-1334. doi:10.1093/jnci/djm120
Sheikh AF, Yadyad MJ, Goodarzi H, Hashemi SJ, Aslani S, Assarehzadegan MA, et al. CagA and vacA allelic combination of Helicobacter pylori in gastroduodenal disorders. Microb Pathog. 2018;122:144-150. doi:10.1016/j.micpath.2018.06.023
Hatakeyama M. Structure and function of helicobacter pylori caga, the first-identified bacterial protein involved in human cancer. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(4):196-219. doi:10.2183/pjab.93.013
Gorrell RJ, Zwickel N, Reynolds J, Bulach D, Kwok T. Helicobacter pylori CagL Hypervariable Motif: a Global Analysis of Geographical Diversity and Association with Gastric Cancer Downloaded from. J Infect Dis. 2016;213(12):1927-1931.
Román-Román A, Martínez-Santos VI, Castañón-Sánchez CA, Albañil-Muñoz AJ, González-Mendoza P, Soto-Flores DG, et al. CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis. Gut Pathog. 2019;11(1). doi:10.1186/s13099-019-0286-9
Yadegar A, Mohabati Mobarez A, Zali MR. Genetic diversity and amino acid sequence polymorphism in Helicobacter pylori CagL hypervariable motif and its association with virulence markers and gastroduodenal diseases. Cancer Med. 2019;8(4):1619-1632. doi:10.1002/cam4.1941
Quach DT, Vilaichone RK, Van Vu K, Yamaoka Y, Sugano K, Mahachai V. Helicobacter pylori infection and related gastrointestinal diseases in southeast Asian countries: An expert opinion survey. Asian Pacific Journal of Cancer Prevention. 2018;19(12):3565-3569. doi:10.31557/APJCP.2018.19.12.3565
Quach DT, Mai BH, Tran MK, Dao LV, Tran HV, Vu KT, et al. Vietnam Association of Gastroenterology (VNAGE) consensus on the management of Helicobacter pylori infection. Front Med (Lausanne). 2023;9. doi:10.3389/fmed.2022.1065045
Tran VH, Nguyen TMN, Le PTQ, Nguyen THT, Nguyen TCL, Ha TMT. Current status of Helicobacter pylori resistance to clarithromycin and levofloxacin in Vietnam: Results from molecular analysis of gastric biopsy specimens. J Glob Antimicrob Resist. 2023;36:76-82. doi:10.1016/j.jgar.2023.12.026
Le NT, Van Nguyen T, Le LT, Nguyen LC. Dietary protein intake and stomach cancer, insights from a case-control study. Sci Rep. 2025;15:6909. doi:10.1038/s41598-024-80793-5
Jones KR, Whitmire JM, Merrell DS. A tale of two toxins: Helicobacter pylori CagA and VacA modulate host pathways that impact disease. Front Microbiol. 2010;1(NOV). doi:10.3389/fmicb.2010.00115
Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7(11):629-641. doi:10.1038/nrgastro.2010.154
Zhu X, Zhao Y, Zhu C, Wang Y, Liu Y, Su J. Rapid detection of cagA-positive Helicobacter pylori based on duplex recombinase aided amplification combined with lateral flow dipstick assay. Diagn Microbiol Infect Dis. 2022;103(1):115661. doi:10.1016/J.DIAGMICROBIO.2022.115661
Maeda S, Yoshida H, Kanai F, Ikenoue T, Kato N, Shiratori Y, et al. Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan. Gut. 1998;42:338-343. doi:10.1136/gut.42.3.338
Yamaoka Y, Kodama T, Gutierrez O, Kim JG, Kashima K, Graham DY. Relationship between Helicobacter priori iceA, cagA, and vacA status and clinical outcome: Studies in four different countries. J Clin Microbiol. 1999;37(7):2274-2279. doi:10.1128/jcm.37.7.2274-2279.1999
Chomvarin C, Namwat W, Chaicumpar K, Mairiang P, Sangchan A, Sripa B, et al. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients. International Journal of Infectious Diseases. 2008;12(1):30-36. doi:10.1016/j.ijid.2007.03.012
Nguyen TMN, Tran VH, Ha TMT. Helicobacter pylori cagA, vacA, and iceA genotypes and clinical outcomes: a cross-sectional study in central Vietnam. Brazilian Journal of Microbiology. 2024. doi:10.1007/s42770-024-01328-8
Nguyen TH, Ho TTM, Nguyen-Hoang TP, et al. The endemic Helicobacter pylori population in Southern Vietnam has both South East Asian and European origins. Gut Pathog. 2021;13(1). doi:10.1186/s13099-021-00452-2
Thai THN, Nguyen HP, Nguyen THY, Nguyen TBH, Nguyen TH, Nguyen TMN, et al. Genetic diversity of the oipA gene among Helicobacter pylori isolates and clinical outcome in Vietnam. Infection, Genetics and Evolution. 2023;112. doi:10.1016/j.meegid.2023.105438
Nguyen TL, Uchida T, Tsukamoto Y, Trinh DT, Ta L, Mai BH, et al. Helicobacter pylori infection and gastroduodenal diseases in Vietnam: A cross-sectional, hospital-based study. BMC Gastroenterol. 2010;10:no pagination. doi:10.1186/1471-230X-10-114
Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis: the updated Sydney system. Am J Surg Pathol. 1996;20(10):1161-1181.
Kushima R, Lauwers GY, Rugge M. Gastric dysplasia. In: WHO Classification of Tumours Editorial Board, ed. WHO Classification of Tumours: Digestive Systemic Tumours. Lyon: International Agency for Research on Cancer; 2019:71-75.
Peek RM, Miller GG, Tham KT, Pé GI, Rez RP, Cover TL, et al. Detection of Helicobacter pylori Gene Expression in Human Gastric Mucosa. J Clin Microbiol. 1995;33(1):28-32. https://journals.asm.org/journal/jcm.
Bickley J, Owen RJ, Fraser AG, Pounder RE. Evaluation of the polymerase chain reaction for detecting the urease C gene of Helicobacter pylori in gastric biopsy samples and dental plaque. J Med Microbiol. 1993;39(5):338-344.
Tran VH, Ha TMT, Le PTQ, Nguyen VN, Phan TN, Paglietti B. Helicobacter pylori 23S rRNA gene mutations associated with clarithromycin resistance in chronic gastritis in Vietnam. The Journal of Infection in Developing Countries. 2018;12(7):526-532. doi:10.3855/JIDC.10000
Jones KR, Joo YM, Jang S, Yoo YJ, Lee HS, Chung IS, et al. Polymorphism in the cagA EPIYA motif impacts development of gastric cancer. J Clin Microbiol. 2009;47(4):959-968. doi:10.1128/JCM.02330-08
Yamaoka Y, Malaty HM, Michael SO, Graham DY. Conservation of Helicobacter pylori Genotypes in Different Ethnic Groups in Houston, Texas. J Infect Dis. 2000;181:2083-2086.
Phan TN, Santona A, Tran VH, Tran TNH, Le VA, Cappuccinelli P, et al. Genotyping of Helicobacter pylori shows high diversity of strains circulating in central Vietnam. Infection, Genetics and Evolution. 2017;52:19-25. doi:10.1016/j.meegid.2017.04.014
Truong BX, Mai VTC, Tanaka H, Ly LT, Thong TM, Hai HH, et al. Diverse characteristics of the cagA gene of Helicobacter pylori strains collected from patients from Southern Vietnam with gastric cancer and peptic ulcer. J Clin Microbiol. 2009;47(12):4021-4028. doi:10.1128/JCM.00504-09
Yeh YC, Cheng HC, Yang HB, Chang WL, Sheu BS. H. pylori CagL-Y58/E59 Prime Higher Integrin α5β1 in Adverse pH Condition to Enhance Hypochlorhydria Vicious Cycle for Gastric Carcinogenesis. PLoS One. 2013;8(8). doi:10.1371/journal.pone.0072735
Wiedemann T, Hofbaur S, Loell E, Rieder G. A C-terminal coiled-coil region of CagL is responsible for Helicobacter pylori-induced IL-8 expression. Eur J Microbiol Immunol (Bp). 2016;6(3):186-196. doi:10.1556/1886.2016.00020
Conradi J, Tegtmeyer N, Wozna M, Wissbrock M, Michalek C, Gagell C, et al. An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA. Front Cell Infect Microbiol. 2012;2(70):1-11. doi:10.3389/fcimb.2012.00070
Barden S, Niemann HH. Adhesion of several cell lines to helicobacter pylori CagL Is mediated by integrin αvβ6 via an rgdlxxl motif. J Mol Biol. 2015;427(6):1304-1315. doi:10.1016/j.jmb.2015.01.006
Bönig T, Olbermann P, Bats SH, Fischer W, Josenhans C. Systematic site-directed mutagenesis of the Helicobacter pylori CagL protein of the Cag type IV secretion system identifies novel functional domains. Sci Rep. 2016;6. doi:10.1038/srep38101
Yeh YC, Chang WL, Yang HB, Cheng HC, Wu JJ, Sheu BS. H. pylori cagL amino acid sequence polymorphism Y58E59 induces a corpus shift of gastric integrin α5β1 related with gastric carcinogenesis. Mol Carcinog. 2011;50(10):751-759. doi:10.1002/mc.20753
Caliskan R, Polat Sari S, Ercan B, Peker, KD, Omac-Sonmez M, Akgul O, et al. New CagL Amino Acid Polymorphism Patterns of Helicobacter pylori in Peptic Ulcer and Non-Ulcer Dyspepsia. Medicina (Lithuania). 2022;58(12). doi:10.3390/medicina58121738
Ogawa H, Iwamoto A, Tanahashi T, Okada R, Yamamoto K, Nishiumi S, et al. Genetic variants of Helicobacter pylori type IV secretion system components CagL and CagI and their association with clinical outcomes. Gut Pathog. 2017;9(1). doi:10.1186/s13099-017-0165-1
Choi YH, Lai J, Kim MA, Kim A, Kim J, Su H, et al. CagL polymorphisms between East Asian and Western Helicobacter pylori are associated with different abilities to induce IL-8 secretion. Journal of Microbiology. 2021;59(8):763-770. doi:10.1007/s12275-021-1136-2
Yeh YC, Kuo HY, Chang WL, Yang HB, Lu CC, Cheng HC, et al. H. pylori isolates with amino acid sequence polymorphisms as presence of both HtrA-L171 & CagL-Y58/E59 increase the risk of gastric cancer. J Biomed Sci. 2019;26(1). doi:10.1186/s12929-019-0498-9
Glatzová D, Mavila H, Saija MC, Chum T, Cwiklik L, Brdička T, et al. The role of prolines and glycine in the transmembrane domain of LAT. FEBS Journal. 2021;288(13):4039-4052. doi:10.1111/febs.15713
Pace CN, Scholtz JM. A Helix Propensity Scale Based on Experimental Studies of Peptides and Proteins. Biophys J. 1998;75:422-427.