<i>dupA</i>
            <sub>1</sub>
            Is Associated with Duodenal Ulcer and High Interleukin-8 Secretion from the Gastric Mucosa

Hussein, Nawfal R.; Abdullah, Shahlaa M.; Salih, Azad; Assafi, Mahde Saleh

doi:10.1128/iai.00076-12

Cited by 4 publications

(9 citation statements)

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“…In our study, we have found the rate of frameshift mutations along the length of dupA gene was [34% (17/50)] high in the Indian population. Similar trend has also been observed in other populations [ 19 , 20 , 24 ]. On the other hand, 66% (33/50) of the dupA positive strains had no stop codon and were considered as intact dupA known as dupA1 .…”

Section: Discussionsupporting

confidence: 90%

“…On the other hand, 66% (33/50) of the dupA positive strains had no stop codon and were considered as intact dupA known as dupA1 . In consistent with the findings of the other studies, the intact dupA ( dupA1 ) without frameshift mutation was significantly associated with DU in the Indian population [ 20 , 24 ]. This result reflects that the detection of dupA by PCR is not adequate to identify an intact dupA because frameshift mutation is common along the length of gene.…”

Section: Discussionsupporting

confidence: 90%

“…In our population, intact dupA1 (long type or short type) with vir genes cluster was not important in promoting DU formation, which is not comparable to the one reported by Jung et al [ 23 ] where the intact dupA cluster was associated with DU . This trend can be linked to our earlier finding in which we have showed that the Indian H. pylori strains are genetically distinct from Western and East Asian strains and the intact cag- PAI from Kolkata has not associated with disease outcome [ 7 , 24 ]. One study showed that none of the strains from Iraq had all six vir gene homologues, but the gene dupA1 was found to be significantly associated with DU [ 28 ].…”

Section: Discussionmentioning

confidence: 72%

“…This finding is in accordance with the observation of Hussein et al . [ 24 ] in the Iraqi population, which showed that IL-8 production was significantly higher in intact dupA1 strain than truncated dupA2 or dupA negative strains. Our study showed that H. pylori strains containing cagA and vacA can induce IL-8 in cell line assay.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study reported that dupA and adjacent 6 vir genes homologues ( virB8 , virB9 , virB10 , virB11 , virD2 and virD4 ) in the plasticity region predicting to form a third T4SS ( tfs3a ) [ 22 ] termed as “ dupA cluster” ( dupA along with six surrounding gene) has been associated with DU in the United States population [ 23 ]. However, the functional role of this dupA cluster in endorsing the DU formation in the Iraqi population is not very clear [ 24 ]. It is well known that the Indian H. pylori strains are genetically distinct than East Asian and Western strains [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population

et al. 2015

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BackgroundThe duodenal ulcer promoting gene (dupA) and dupA cluster in Helicobacter pylori have been described as a risk factor for duodenal ulcer development in some populations. Polymorphic gene dupA can be divided into two groups, intact dupA1 (long or short type based on the presence or absence of 615-bp extra sequences at the 5′ region) having complete reading frame and other truncated dupA2 having frame-shift mutation. This study was aimed to elucidate the role of dupA of H. pylori and their clusters in the disease manifestation of Indian population.MethodsA total of 170 H. pylori strains were screened for the presence of dupA, dupA alleles and dupA cluster by PCR and sequencing. Pro-inflammatory cytokine (IL-8) with different dupA variant H. pylori stimulated gastric epithelial cells (AGS cells) was measured by ELISA.ResultsA total of 50 strains (29.4%) were positive for dupA among the tested 170 strains. The prevalence of dupA1 in duodenal ulcer (DU) and non-ulcer dyspepsia (NUD) populations was found to be 25.5% (25/98) and 11.1% (8/72), respectively and 16.4% (28/170) of the tested strains had dupA1, cagA and vacAs1m1 positive. The distribution of long and short type dupA1 has not been significantly associated with the disease outcome. The dupA cluster analysis showed that 10.2% (10/98) and 8.3% (6/72) strains were positive among DU and NUD, respectively. IL-8 production was significantly higher in dupA1+, cagA+, vacA+ (902.5 ± 79.01 pg/mL) than dupA2+, cagA+, vacA+ (536.0 ± 100.4 pg/mL, P = 0.008) and dupA−, cagA+, vacA+ (549.7 ± 104.1 pg/mL, P = 0.009). Phylogenetic analysis of dupA indicated that the Indian H. pylori strains clustered with East Asian strains but distinct from Western strains. This is the first known genetic element of Indian H. pylori that is genetically closer to the East Asian strains but differed from the Western strains.ConclusionsThe intact dupA1 was significantly associated with DU than NUD (P = 0.029) but the dupA1 cluster has no role in the disease manifestation at India (P = 0.79). Thus, dupA1 can be considered as a biomarker for DU patients in India.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population

et al. 2015

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Helicobacter pylori dupA and smoking are associated with increased levels of interleukin-8 in gastric mucosa in Iraq

Hussein

Tuncel

2015

Human Pathology

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

Hussein

Tunjel

Majed

et al. 2015

New Microbes and New Infections

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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.

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dupA ₁ Is Associated with Duodenal Ulcer and High Interleukin-8 Secretion from the Gastric Mucosa

Cited by 4 publications

References 4 publications

Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population

Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population

Helicobacter pylori dupA and smoking are associated with increased levels of interleukin-8 in gastric mucosa in Iraq

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

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dupA 1 Is Associated with Duodenal Ulcer and High Interleukin-8 Secretion from the Gastric Mucosa

Cited by 4 publications

References 4 publications

Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population

Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population

Helicobacter pylori dupA and smoking are associated with increased levels of interleukin-8 in gastric mucosa in Iraq

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

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dupA ₁ Is Associated with Duodenal Ulcer and High Interleukin-8 Secretion from the Gastric Mucosa