Helicobacter pylori cagL amino acid polymorphism D58E59 pave the way toward peptic ulcer disease while N58E59 is associated with gastric cancer in north of Iran

Cherati, Mina Rezaee; Shokri‐Shirvani, Javad; Karkhah, Ahmad; Rajabnia, Ramazan; Nouri, Hamid Reza

doi:10.1016/j.micpath.2017.04.025

Cited by 19 publications

(19 citation statements)

References 20 publications

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“…This is a lower percentage than those found in Asian patients, > 85% in Chinese, Indian, Iranian, Taiwanese and Malay patients [20, 21, 30, 31]; however, these patients had more severe diseases, like gastric cancer, peptic ulcer disease, and duodenal ulcer. Nevertheless, our result is higher to that found in Iranian patients with gastritis (64.2%) [32]. Apparently, the prevalence of cagL in clinical isolates from patients with gastritis is lower than that found in isolates from patients with peptic ulcer disease or gastric cancer.…”

Section: Discussioncontrasting

confidence: 89%

“…However, our results showed that D58/K59 was the most common polymorphism in Mexican patients with chronic gastritis and it is associated with the vacA genotype s1/m1. We also found a high frequency of the polymorphisms M60 (85%), which has been previously shown to increase the chance of developing gastritis [32], and E62 (81.8%), which has been shown to be the most common polymorphism in strains from Iranian patients with chronic gastritis [32]. It is worth noting that in this region the only invariable residue is G61.…”

Section: Discussionsupporting

confidence: 69%

“…It has been proposed that strains carrying aspartic acid at this position lead to a lower risk of gastric cancer in comparison with the asparagine carrying strains. In agreement with this, the polymorphism N58 was significantly associated with gastric cancer in Mexican patients from Mexico City [22, 32]. Regarding residue combinations in positions 58 and 59, polymorphism D58/K59 has been associated with gastric cancer in India, where patients carrying bacteria with this polymorphism are 3.8 times more likely to develop this disease [20].…”

Section: Discussionmentioning

confidence: 70%

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CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis

et al. 2019

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Background: Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa in humans. One of the main virulence factors of H. pylori is the cag pathogenicity island (cagPAI), which encodes a type 4-secretion system (T4SS) and the cytotoxin CagA. Translocation of CagA through the T4SS triggers host-signaling pathways. One of the T4SS proteins is CagL, which is necessary for CagA translocation. CagL is a 26-kDa protein that contains a hypervariable motif, which spans residues 58 to 62. Several polymorphisms in this region have been associated with different disease outcomes, e.g. in Mexico, N58 is associated with a higher risk of gastric cancer. The aim of this work is to analyze the sequence of the hypervariable motif (residues 58 to 62) of clinical isolates from Mexican patients with chronic gastritis, and to correlate these polymorphisms with the vacA genotype. Results: Of the 164 biopsies analyzed, only 30.5% (50/164) were positive for H. pylori. Thirty-six of the 50 clinical isolates (72%) were cagA positive, and 40 (80%) had the most virulent vacA genotype (s1/m1). Of the cagA positive strains, 94.4% were vacA s1/m1. All the cagA + strains contained the cagL gene. The most prevalent sequence in the polymorphic region (residues 58-62) was DKMGE (75.8%, 25/33), followed by NKMGQ and NEIGQ (6.1%, 2/33), and DEIGQ, NKMGE, DKIGE, and DKIGK (3%, 1/33). Regarding polymorphisms in positions 58 and 59, the most common were D58/K59 (81.8%, 27/33), followed by N58/K59 (9.1%, 3/33), and D58/E59 (3%, 1/33). Only two isolates (6.1%) contained residues N58/E59, which correspond to those found in H. pylori strain ATCC 26695. 92.6% of the clinical isolates having polymorphism D58/K59 had the genotype vacA s1/m1, considered to be the most virulent, while 7.4% had the genotypes vacA s1/m2 and s2/m2. Conclusions: In Mexican patients, CagL polymorphisms D58, K59, M60, E62, K122, and I134 are more common in patients with chronic gastritis.

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Section: Discussioncontrasting

confidence: 89%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 70%

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CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis

et al. 2019

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“…The H. pylori isolates with CagL amino acid polymorphisms as Y58/E59 exploit higher integrin α5β1 to carry 4.6-fold risk increase of gastric cancer [4]. Studies analyzed Asian and non-Asian subject cohorts were consistent with our finding to show that CagL-E59 was associated with gastric cancer [12–14]. Moreover, we previous reported H. pylori CagL-Y58/E59 can prime higher integrin α5β1 in adverse pH condition to enhance hypochlorhydria vicious cycle for gastric carcinogenesis [15].…”

Section: Introductionsupporting

confidence: 86%

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

et al. 2019

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BackgroundH. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59.MethodsOne-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing.ResultsThe prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1–6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001).ConclusionsThe H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer.Electronic supplementary materialThe online version of this article (10.1186/s12929-019-0498-9) contains supplementary material, which is available to authorized users.

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“…To date, Hp genotyping on biopsy specimens has been almost limited to CagA EPIYA motif patterns 32 . There are more recent studies based on sequencing technology, reporting associations between specific Hp genetic variants and clinical phenotypes 33‐37 . However, these sequencing studies have been performed on a limited number of samples and with Hp strains isolated from the patients.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high‐grade premalignant gastric lesions

Canzian

Rizzato

Obazee

et al. 2020

Intl Journal of Cancer

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Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high‐risk population groups.

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Helicobacter pylori cagL amino acid polymorphism D58E59 pave the way toward peptic ulcer disease while N58E59 is associated with gastric cancer in north of Iran

Cited by 19 publications

References 20 publications

CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis

CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis

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

Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high‐grade premalignant gastric lesions

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