Clinical Relevance and Diversity of Two Homologous Genes Encoding Glycosyltransferases in Helicobacter pylori

摘要

Helicobacter pylori is known to be a major cause of peptic ulceration. The jhp0562 gene, encoding a glycosyltransferase involved in the synthesis of the lipopolysaccharide, was associated with peptic ulcer disease (PUD) in children. The β-(1,3)-galactosyltransferase [β-(1,3)GalT] gene (jhp0563), involved in Lewis (Le) antigen expression, is highly similar to jhp0562. The clinical significance and diversity of both genes were examined by PCR and sequencing of clinical strains (n = 117) isolated from children with PUD (n = 57) and nonulcer dyspepsia (NUD; n = 60). The prevalence of the jhp0562 gene was significantly higher in strains with a more-virulent profile (strains positive for the cag pathogenicity island [PAI], vacA sl allele, babA, homB, phase-variable gene oipA “on” [i.e., functional], and hopQ I allele). The distribution of genotypes according to clinical outcome showed that the presence of jhp0562 represented one of the greatest risks for the development of PUD. Moreover, the triple-positive genotype for the cag PAI, jhp0562, and homB provided the best discriminatory model for distinguishing PUD and NUD outcomes in children. Sequence and in vitro expression analyses of jhp0562 showed the presence of a complete open reading frame, while the β-(1,3)GalT gene was shown to be a phase-variable gene. The regular presence of jhp0562 in strains with a truncated β-(1,3)GalT gene suggests that jhp0562 may also be implicated in the regulation of Le antigen expression. Overall, the results of this study suggest that the jhp0562 gene is of great clinical relevance, being a useful comarker for severe H. pylori-related disease and contributing to host adaptation.