Allelic Variation of Helicobacter pylori babA and cagA Genes and their Association with Clinical Consequences

Abstract

Helicobacter pylori (H. pylori) is classified as a class I carcinogen. The low infection rate seen in developed countries (8.9%) compared with a high infection rate (52%-98%) in developing countries indicates a strong association between infection prevalence and socioeconomic status. Adhesion of H. pylori to gastric epithelial cells is an important aggressive factor. One of the genes that encodes for an adhesive protein is babA2, which facilitates the location of bacteria on gastric epithelial cells and delivery of toxic proteins (CagA, VacA) into the host cells. BabA2 is a 78 KD protein that binds to the Le^b antigens on gastric epithelial cells. Some studies have shown an association between babA2 and peptic ulcer disease or gastric cancer. The cagA gene which encodes an immunodominant protein has a mosaic structure composed of protected and various regions. The C-terminal region of CagA, which includes multiple numbers of EPIYA (Glu-Pro-Ile-Tyr-Ala) motifs, is tyrosine-phosphorylated. Western and East Asian strains represent EPIYA-C and EPIYA-D motifs, respectively. The C- and D- types serve as low-affinity and high-affinity SHP-2-binding sites and interfere with SHP-2 phosphatase activity. A majority of East Asian strains have shown strong conservation and lack of duplication in the D region while the Western strains have shown multiple numbers of the EPIYA-C motif, which increase gastric cancer risk. CagA, either tyrosine-phosphorylated (in its C-terminal motifs) or not in host cells, alters the expression of certain genes to cause gastric cancer. The importance of these genes in predicting clinical outcomes is related to the phylogeographical origins of the bacterium. If the mechanisms by which H. pylori causes cancer are elucidated, they can assist in achieving effective strategies for the prevention and treatment of gastric cancer.