**4. The PZ-associated gene** *jhp0940* **and its relationship with gastroduodenal disease**

The prevalence of the *jhp0940* gene in various *H. pylori* isolates from different geographical regions has been explored (**Figure 2**). Studies have reported varying results regarding its prevalence and association with disease, and the presence of this gene has even been suggested to be related to a lower risk of peptic ulcers or gastric cancer [21, 22]. In a genotyping study of *H. pylori* isolates from Mexican individuals with gastroduodenal diseases, *jhp0940* was absent in all gastric cancer isolates [16]. In Brazil, in patients with duodenal ulcers or gastric cancer, the presence of *jhp0940* in *H. pylori* isolates exhibited no association with disease, as only 3 of 200 isolates had

**Figure 2.** Frequency of the presence of the *jhp0940*, *jhp0945*, *jhp0947* and *jhp0949* genes among *H. pylori* isolates from different geographical regions. Frequencies are based on the following reports: USA, Colombia, South Korea [21]; Japan [21, 25]; Netherlands [32]; Iran [28]; India [22, 25]; Pakistan [27]; China [24]; Costa Rica [30, 25]; Brazil [23]; Argentina [26]; Peru [25]; South Africa [25]; France [25]; Spain [25]; and Mexico [16, 29].

the gene [23]. In addition, no association was found between this gene and disease in isolates from Chinese patients with chronic active gastritis, duodenal ulcers or gastric cancer [24].

that are flanked by discrete sequences of 5′AAGAATG and are each referred to as a TnPZ or "transposon, plasticity zone". Each TnPZ generally contains genes encoding type IV secretion proteins (tfs3), *xerT*, an ORF coding for a protein with helicase and DNA methylase domains and additional ORFs. Among the studied strains, several types of TnPZs with different gene arrangements or DNA sequence variations were observed and classified as type 1, type 1b and type 2 TnPZs. The genes *jhp0945*, *jhp0947* and *jhp0949* are located on a type 1b TnPZ, and

The prevalence of the *jhp0940* gene in various *H. pylori* isolates from different geographical regions has been explored (**Figure 2**). Studies have reported varying results regarding its prevalence and association with disease, and the presence of this gene has even been suggested to be related to a lower risk of peptic ulcers or gastric cancer [21, 22]. In a genotyping study of *H. pylori* isolates from Mexican individuals with gastroduodenal diseases, *jhp0940* was absent in all gastric cancer isolates [16]. In Brazil, in patients with duodenal ulcers or gastric cancer, the presence of *jhp0940* in *H. pylori* isolates exhibited no association with disease, as only 3 of 200 isolates had

**Figure 2.** Frequency of the presence of the *jhp0940*, *jhp0945*, *jhp0947* and *jhp0949* genes among *H. pylori* isolates from different geographical regions. Frequencies are based on the following reports: USA, Colombia, South Korea [21]; Japan [21, 25]; Netherlands [32]; Iran [28]; India [22, 25]; Pakistan [27]; China [24]; Costa Rica [30, 25]; Brazil [23]; Argentina [26];

Peru [25]; South Africa [25]; France [25]; Spain [25]; and Mexico [16, 29].

*jhp0940* is located on a type 2 TnPZ in strain J99 (see **Figure 1**).

80 Helicobacter Pylori - New Approaches of an Old Human Microorganism

**gastroduodenal disease**

**4. The PZ-associated gene** *jhp0940* **and its relationship with** 

A study in India observed less than a 20% prevalence of the *jhp0940* gene among *H. pylori* isolates [22]. However, in other isolates from India, the reported *jhp0940* prevalence was higher than 80% [25]. In Argentina, the frequency of the *jhp0940* gene was reported as 74.6%, and the frequency in isolates from individuals with chronic gastritis and peptic ulcer disease was similar, indicating no association with a specific disease [26]. However, Rizwan et al. [25] found no relationship between clinical results and the prevalence of *jhp0940* or the cag PAI in isolates from seven countries (India, South Africa, Japan, Costa Rica, Peru, France and Spain). The highest prevalence of this gene was observed in isolates from India, South Africa and France, in contrast to isolates from Spain, where less than 10% contained this gene.

However, Yakoob et al. [27] and Gholizade Tobnagh et al. [28] reported an association between *jhp0940* and gastric ulcers and gastric cancer, respectively. In general, the prevalence of this gene is lower than that of *jhp0945*, *jhp0947* and *jhp0949* in isolates from the different geographical regions that have been studied. There appears to be a difference between the presence of PZ genes between isolates from children and adults. Romo-González et al. [29] observed that the prevalence of *jhp0940* in *H. pylori* isolates from children is higher than that in adults and that the presence of the specific gene patterns (including *jhp0940-jhp0945-jhp0947*-*jhp0949* and *jhp0940*-*jhp0947*-*jhp0949*) is more common in isolates from children than in adults. Therefore, these authors suggest that this locus is more integrated in the early stages of infection, which could contribute to the bacterial virulence and evolution of the infection. These authors found no association between the presence of these four PZ-associated genes and the presence of *cagA*, cag PAI or *dupA*.

Romo-González et al. evaluated the *in vitro* expression of four PZ-associated genes in isolates from children and adults and observed the expression of only *jhp0945*, *jhp0947* and *jhp0949*, without significant differences among the expression of these three genes between the isolates obtained from children and adults. However, a correlation was observed among the expression of these three genes (unpublished data).

A possible explanation for the discordant results regarding the prevalence of *jhp0940* in different geographical regions is that geographical diversity exists in the sequence of this gene that does not allow for its identification with a single pair of primers. Another potential reason is that the absence of this gene in adult isolates is due to the loss of this gene during infection.
