LETTER
We read with interest the recent article by Jung et al. addressing the relationship of the dupA gene cluster with clinical outcomes and gastric mucosal interleukin 8 (IL-8) secretion (4). It was found that Helicobacter pylori infection with strains possessing a complete dupA cluster increased duodenal ulcer risk compared to that with H. pylori infection with strains with an incomplete dupA cluster or without the dupA gene. Findings were independent of the cag pathogenicity island (PAI) status. It was also found that gastric mucosal IL-8 levels were significantly higher in the complete dupA cluster group than in the incomplete dupA cluster group or the group without the dupA gene (4).
Using the same methodology described in Jung et al., we studied the relationship between dupA cluster genes, clinical outcomes, and gastric mucosal IL-8 levels in 68 (22 duodenal ulcer [DU], 5 gastric ulcer [GU], 41 nonulcer dyspepsia [NUD]) Iraqi samples. The prevalence of dupA was 48.4% (33/68), and those of other vir gene homologues were 76.5% for virB8 (52/68), 57.4% for virB9 (39/68), 67.6% for virB10 (46/68), 77.9% for virB11 (53/68), 52.9% for virD4 (36/68), and 73.5% for virD2 (50/68) (Table 1). In contrast with Jung et al.'s report, none of the H. pylori strains possessed all 6 vir gene homologues. We did not observe associations between the presence of the dupA gene and clinical outcomes; this result is consistent with results from other countries, such as Brazil and Iran (1, 3). As dupA was previously classified into dupA1 (functional) and dupA2 (nonfunctional, including the original form described in which the open reading frame was broken by a stop codon) (2), we sequenced dupA genes from a collection of H. pylori strains isolated in Iraq as described previously (2). A total of 33% (11/33; 8 DU, 0 GU, 3 NUD) of dupA-positive Iraqi strains typed as dupA1. A significant association was observed between dupA1 and DU (P < 0.01). This result may indicate that dupA1 is important in DU development. Therefore, dupA polymorphisms may explain the contradictory association between dupA and clinical outcomes, and this may be more important than an intact dupA gene cluster.
Table 1.
The prevalence of dupA and vir genes in 68 Iraqi strainsa
| Gene | No. of strains (%) in each group containing the indicated gene |
|||
|---|---|---|---|---|
| All | DU | GU | NUD | |
| virB8 | 52 (76.5) | 19 (86.4) | 5 (100.0) | 28 (68.3) |
| virB9 | 39 (57.4) | 13 (59.1) | 3 (60.0) | 23 (56.1) |
| virB10 | 46 (67.6) | 15 (68.2) | 1 (20.0) | 30 (73.2) |
| virB11 | 53 (77.9) | 15 (68.2) | 5 (100.0) | 33 (80.5) |
| virD4 | 36 (52.9) | 14 (63.6) | 2 (40.0) | 20 (48.8) |
| virD2 | 50 (73.5) | 13 (59.1) | 1 (20.0) | 36 (87.8) |
| dupA | 33 (48.5) | 12 (54.5) | 2 (40.0) | 19 (46.3) |
The 68 strains were composed of 22 DU, 5 GU, and 41 NUD.
Additionally, we studied gastric mucosal levels of IL-8. We classified our patients into 3 groups according to dupA status: patients carrying dupA1 strains, those with dupA2 strains, and those with dupA-negative strains. Gastric mucosal IL-8 levels were significantly higher in patients carrying dupA1 strains than in the other groups (dupA1, 55.6 ± 8.6 pg/mg; dupA2, 27 ± 1.7 pg/mg; dupA negative, 28.6 ± 3.4 pg/mg; P < 0.05) (Fig. 1). These findings suggest that dupA1 is important in IL-8 production in the gastric mucosa.
Fig 1.
IL-8 secretion from the gastric mucosas of patients infected with H. pylori. Error bars indicate the standard deviation. Gastric mucosal IL-8 levels were significantly higher in patients carrying dupA1 than in other groups.
In conclusion, classification of dupA into dupA1 (functional) and dupA2 (nonfunctional), rather than either dupA status or the presence of an intact dupA gene cluster, correlates with clinical outcome and gastric IL-8 levels in Iraqi H. pylori infection. Further research is needed to investigate the role of dupA in H. pylori-associated disease development.
ACKNOWLEDGMENTS
We are grateful to John Atherton and Karen Robinson for their help and support during this work. We thank Karwan Fendi and Halat Majed for their excellent technical assistance.
We have no conflicts of interest to declare.
Contributor Information
Nawfal R. Hussein, Clinical Microbiology and Infection Control Department, Azadi Teaching Hospital and the Department of Microbiology, School of Medicine, Faculty of Medical Sciences, University of Duhok, Kurdistan Region, Iraq
Shahlaa M. Abdullah, Genomic Centre, Koya University, Koya, Kurdistan Region, Iraq
Azad M. Salih, Clinical Microbiology and Infection Control Department, Azadi Teaching Hospital and the Department of Microbiology, School of Medicine, Faculty of Medical Sciences, University of Duhok, Kurdistan Region, Iraq
Mahde A. Assafi, The Centre for Biomolecular Sciences, University of Nottingham, Nottingham, United Kingdom
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