Epidemiological Link between Gastric Disease and Polymorphisms in VacA and CagA

Abstract

Gastritis, peptic ulcer disease, and gastric cancer are a few of the diverse disease manifestations that have been shown to be associated with infection by Helicobacter pylori. Why some individuals develop more severe forms of disease remains largely unknown. In this study, 225 South Korean strains were genotyped for vacA and then analyzed to determine if particular genotypes varied across disease state, sex, or cagA allele. Of these strains, 206 strains carried an s1/i1/m1 allele, 11 strains carried an s1/i1/m2 allele, and 8 strains carried an s1/i2/m2 allele. By using Fisher's exact test, a statistical association between variations in the cagA and vacA alleles was identified (P ‫؍‬ 0.0007), and by using log linear modeling, this variation was shown to affect the severity of disease outcome (P ‫؍‬ 0.027). Additionally, we present evidence that variation within the middle region of VacA contributes significantly to the distribution of vacA alleles across gender (P ‫؍‬ 0.008) as well as the association with disease outcome (P ‫؍‬ 0.011). In this South Korean population, the majority of H. pylori strains carry the vacA s1/i1/m1 allele and the CagA EPIYA-ABD allele. These facts may contribute to the high incidence of gastric maladies, including gastric cancer.

The Geographic Origin of Helicobacter pylori Influences the Association of the homB Gene with Gastric Cancer

“…Our studies showed that there is a significant association between infection with H. pylori strains carrying the EPIYA-ABD cagA genotype and the development of gastric cancer (11). Moreover, the majority of H. pylori isolates encoded the most virulent CagA (EPIYA-ABD) and VacA (s1/i1/m1) proteins (9,11). The polymorphisms in cagA and vacA, alone and in concert, impact the progression to severe gastric disease, but the impact of these two virulence factors alone is not sufficient to explain the vast discrepancy in gastric cancer rates between East Asian and Western populations.…”

“…Clearly, gastric diseases are due, at least in part, to infection by H. pylori, and the ultimate disease developed appears to be affected by variability in H. pylori virulence factors. Recently, we presented detailed epidemiological studies of cagA and vacA from a collection of 260 isolates from South Korea (9,10,11). Our studies showed that there is a significant association between infection with H. pylori strains carrying the EPIYA-ABD cagA genotype and the development of gastric cancer (11).…”

“…The polymorphisms in cagA and vacA, alone and in concert, impact the progression to severe gastric disease, but the impact of these two virulence factors alone is not sufficient to explain the vast discrepancy in gastric cancer rates between East Asian and Western populations. Thus, it is important to examine the impacts of different virulence factors among both Western and East Asian populations (9,10,11,16).…”

Genotype Diversity and Quasispecies Development of <i>Helicobacter pylori</i> in a Single Host

“…In our study, conversion of the vacA alleles, cagA ＋ : cagA -, and iceA1/A2 ＋ : iceA1/2 -was suggested to have occurred in some patients. These virulence factors are presently considered the main proteins involved in pathogenesis of H. pylori and their diversity has been associated with different disease outcomes (29)(30)(31)(32). Results of our study demonstrated the presence of great diversity among the isolates based on genotyping (30.76z); our result was higher than that seen in other reports (21).…”

Analysis of the 3' Variable Region of Cytotoxin-Associated Gene A (&lt;i&gt;cagA&lt;/i&gt;) in &lt;i&gt;Helicobacter pylori&lt;/i&gt; Isolates in China

“…In East Asian countries such as China, Japan, and Korea, the prevalence of H. pylori infection is 60% -88%, and H. pylori-associated gastric cancers occur more frequently than in Western countries [4][5][6]. Many epidemiological studies have suggested that progression from H. pylori infection to adverse effects is controlled by combinations of genetic variants in the host, environmental factors, and H. pylori gene polymorphisms [7][8][9].…”