Characterization of Helicobacter pylori cagA andvacAGenotypes among Alaskans and Their Correlation with Clinical Disease

Abstract

Helicobacter pylori infection is common in Alaska. The development of severe H. pylori disease is partially determined by the virulence of the infecting strain. Here we present vacA and cagA genotype data for H. pylori strains isolated from Alaskans and their correlation with clinical disease. We enrolled patients scheduled for esophagogastroduodenoscopy and positive for H. pylori infection. Gastric biopsy specimens from the stomach antrum and fundus were cultured. We performed PCR analysis of the H. pylori vacA gene and for the presence of the cagA gene and cagA empty site. We genotyped 515 H. pylori samples from 220 Native and 66 non-Native Alaskans. We detected the cagA gene in 242/286 (85%) persons; of 222 strains that could be subtyped, 95% (212) were non-Asian cagA and 3% (6) were East Asian cagA. After removing mixed infections (n ‫؍‬ 17), 83% of H. pylori strains had either the vacA s1m1 (120/269) or s2m2 (103/269) genotype. Sixty-six percent (68/103) of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. Infection with an H. pylori strain having the cagA gene or vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with a decreased risk of esophagitis (P ‫؍‬ 0.003 and 0.0003, respectively). Infection with an H. pylori strain having the vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with an increased risk of peptic ulcer disease (PUD) (P ‫؍‬ 0.003). The majority of H. pylori strains in this study carried the non-Asian cagA gene and either the vacA s1m1 or s2m2 genotype. A majority of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. There was an association of H. pylori genotype with esophagitis and PUD.

Correlation of Helicobacter pylori Genotypes with Gastric Histopathology in the Central Region of a South-European Country

“…babA2 were associated with peptic ulcer. The correlation of such clinical manifestation with these genotypes is consistent with earlier studies [35,41,52]. This is explained by the higher virulence and mucosal injury determined by such strains.…”

“…The H. pylori vacA s1m1 genotype is the most common in American, European and East Asian countries [24,29,[41][42][43]. The vacA s2m2 genotype is apparently less common and another study in Portugal, performed in patients submitted to a screening program, revealed a prevalence of 29.7 % for such allele combination (42.9 % if multiple vacA genotypes were excluded).…”

“…This allelic variant is essentially detected in East Asian patients but some cases were already described in Westerners [7,40,41,48].…”

H. pylori-associated pathologic findings among Alaska native patients

“…The progression from normal tissue to cancerous tissue is thought to be a change from acute gastritis to chronic gastritis to IM to cancer [44,45]. The association seen here, between cagPAI and both IM and moderate–severe acute antral gastritis, agrees with previous reports that have shown an intact element is related to more severe disease [7,11,12,21,46–48]. A previous study in Alaska Native people found that over 90% of both individuals with gastric cancer and healthy individuals had antibodies against the CagA protein[19], indicating that exposure to bacteria expressing and exporting this protein is very common.…”

“…During the EGD, gastric biopsy specimens were also collected for H. pylori culturing and genotyping, as previously described [21,22]. PCR analysis was performed on H. pylori DNA extracts to detect the presence of the right and left ends of the cagPAI , as well as the cagA, cagE, cagT , and virD4 genes (Supplemental Table 1).…”