Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori

Abstract

Helicobacter pylori infection is linked to various gastroduodenal diseases; however, only approximately 20% of infected individuals develop severe diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. Furthermore, the incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors, especially cagA, vacA, and the right end of the cag pathogenicity island. The genotype of the virulence genes is also useful as a tool to track human migration utilizing the high genetic diversity and frequent recombination between different H. pylori strains. Multilocus sequence typing (MLST) analysis using 7 housekeeping genes can also help predict the history of human migrations. Population structure analysis based on MLST has revealed 7 modern population types of H. pylori, which derived from 6 ancestral populations. Interestingly, the incidence of gastric cancer is closely related to the distribution of H. pylori populations. The different incidence of gastric cancer can be partly attributed to the different genotypes of H. pylori circulating in different geographic areas. Although approaches by MLST and virulence factors are effective, these methods focus on a small number of genes and may miss information conveyed by the rest of the genome. Genome-wide analyses using DNA microarray or whole-genome sequencing technology give a broad view on the genome of H. pylori. In particular, next-generation sequencers, which can read DNA sequences in less time and at lower costs than Sanger sequencing, enabled us to efficiently investigate not only the evolution of H. pylori, but also novel virulence factors and genomic changes related to drug resistance.

Prevalence of <i>Helicobacter pylori vacA</i>, <i>cagA</i>, <i>dupA</i> and <i>oipA</i> Genotypes in Patients with Gastric Disease

“…Studies have found that in Western countries, strains containing the s1m1 genotype are associated with a higher risk of gastric disease, as well as with enhanced proinflammatory response [17]. Similar to our results, Asrat, et al [18] and Suzuki, et al [19] also found s1m1 to be the most common vacA genotype. Interestingly, all of these virulence factors have a mutual relationship; for example, cagA-positive strains often have the s1m1 genotype, and several studies have provided evidence of an association between the cagA+/vacA s1m1 genotype and the risk of gastric disease, which was also found in our study [20] [21] [22].…”

Helicobacter pylori vacA d1 Genotype Predicts Risk of Gastric Adenocarcinoma and Peptic Ulcers in Northwestern Iran

“…However, the incidence of gastric cancer is enigmatically low in Africa and South Asia, where frequency of H pylori infection is high. Furthermore, several studies from East Asia and Iran have indicated a tendency towards reduction of GC incidence from north to south within these areas (Suzuki et al, 2012;Latifi-Navid et al, 2013). H pylori virulence factors have been shown to play an important role in determining the course of H pylori associated disease (Suerbaum and Michetti, 2002).…”

The relationship of Cag-A in patients with HP positive alopecia areata and vitiligo

“…Özellikle kronik atrofik gastrit, peptik ülser ve gastrik kanser gibi gastrointestinal sistem hastalıkları başta olmak üzere romatolojik, hematolojik ve dermatolojik hastalıklar gibi birçok gastrointestinal sistem dışı hastalığında etyopatogenezinde suçlanmaktadır (1). Vac-A(vacuolating cytotoxin) ve Cag-A, HP suşları nın ürettiği ve bakteri virulansından sorumlu olan iki önemli sitotoksindir (13). Bu sitotoksinler içinde Cag-A özellikle doğu ülkelerinde dü-şük sıklıkta saptanmaktadır ve gastrointestinal dışı hastalıklar ve komplikasyonlardan temel olarak sorumlu tutulmaktadır (13).…”

“…Vac-A(vacuolating cytotoxin) ve Cag-A, HP suşları nın ürettiği ve bakteri virulansından sorumlu olan iki önemli sitotoksindir (13). Bu sitotoksinler içinde Cag-A özellikle doğu ülkelerinde dü-şük sıklıkta saptanmaktadır ve gastrointestinal dışı hastalıklar ve komplikasyonlardan temel olarak sorumlu tutulmaktadır (13). Literatürde; AA'nın etyolojisinde HP'nin ilişkili olabileceğini gösteren çelişkili sonuçlar bulunmaktadır (14,15).…”