Duodenal ulcer promoting gene 1 (dupA1) is associated with A2147G clarithromycin-resistance mutation but not interleukin-8 secretion from gastric mucosa in Iraqi patients

Abstract

Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma. The aims were to study the influence of dupA1 positivity upon interleukin-8 (IL-8) secretion from gastric mucosa and determine the prevalence of mutations responsible for clarithromycin and fluoroquinolone resistance. DNA was extracted from 74 biopsies and the virulence factors were studied. Levels of IL-8 in gastric mucosa were measured using ELISA and the mutations responsible for clarithromycin and fluoroquinolone resistance were determined using a GenoType-HelicoDR assay. The prevalence of cagA in strains isolated from gastric ulcer (GU) and duodenal ulcer (DU) was significantly higher than those isolated from non-ulcer disease (NUD) (90% and 57.9% versus 33.3%; p 0.01). The vacA s1m1 genotype was more prevalent in patients with DU (73.7%) and GU (70%) than in those with NUD (13.3%) (p 0.01). The prevalence of dupA1 was higher in DU patients (36.8%) than those with GU (10%) and NUD (8.9%) (p 0.01). Multivariate analysis showed that a cagA+/vacA s1i1m2 virulence gene combination was independently associated with the developing peptic ulcer disease (PUD) with increased odds of developing PUD (p 0.03; OR = 2.1). We found no significant difference in the levels of IL-8 secretion in gastric mucosa infected with H. pylori dupA-negative and H. pylori dupA1-positive strains (dupA-negative: mean ± median: 28 ± 26 versus 30 ± 27.1 for dupA1; p 0.6). While 12 strains were clarithromycin resistant, only three isolates were levofloxacin resistant. A significant association was found between dupA1 genotype and A2147G clarithromycin resistance mutation (p <0.01). Further study is needed to explore the relationship between virulence factors and disease process and treatment failure.

VacA and CagA Status as Biomarker of Two Opposite End Outcomes of Helicobacter pylori Infection (Gastric Cancer and Duodenal Ulcer) in a Moroccan Population

“…Unfortunately, there is no data from the North African countries regarding the polymorphism of the three region of vacA . In our study, the determined distribution is almost similar to the one determined among Sicilian and Kenyan patients [ 28 , 31 ] and differs from the others reported among European, Senegalese, Iranian, Malaysian and the South Korean ones, where vacAs1i1m1 was the most predominant genotype [ 8 , 32 – 34 ], while vacA s1i2m2 was the prevalent genotype in Iranian population [ 35 ]. This difference may explain the predominance of severe diseases in these regions.…”

Role ofdupAin virulence ofHelicobacter pylori

“…The observed discrepancy of dupA link with disease outcomes might be associate with the plasticity region of H. pylori or the limitation of PCR to detect the various forms of dupA gene; however, in order to draw a better conclusion further experiments are required[58,59]. Interestingly, the presence of dupA was significantly associated with H. pylori eradication failure with no biologic explanation[60-62]. In conclusion, it sounds that rather than promoting gastric cancer or duodenal ulceration in all populations, dupA is an effective factor for some of populations.…”

Novel virulence factor dupA of Helicobacter pylori as an important risk determinant for disease manifestation: An overview

“…Further studies with H. pylori infected patients showed that cagA , complete dupA cluster and smoking habit were associated with increased levels of IL-8 production from gastric mucosa[ 55 ]. It was also shown in another study that the high IL-8 level in gastric mucosa was neither significantly associated with dupA1 positive strains nor with dupA negative strains[ 56 ]. A significant association has also been found between dupA1 and A2147G clarithromycin resistance mutation.…”