Characterization of Helicobacter pylori cagA and vacA genotypes 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.

Fig. 1.

Proportion of Helicobacter pylori vacA genotypes isolated from Alaska Native and non-Native persons in Alaska from 1998 to 2005. a, numbers within the bars represent the number of persons infected with H. pylori having that vacA genotype; b, P = 0.003 for Alaska Native people versus non-Native people.

Fig. 2.

Percentage of Alaska Native and non-Native persons infected with a cagA-positive strain of Helicobacter pylori stratified by the vacA genotype of their infecting organism in Alaska from 1998 to 2005. Persons with both cagA-positive and cagA-negative H. pylori colonies were considered to be infected with a cagA-positive strain. a, p < 0.0001 for Alaska Native people versus non-Native people.