- The CagA protein of Helicobacter pylori is classified into two main types based on the arrangement of EPIYA motifs: Western-type CagA and East Asian-type CagA.
- Western-type CagA:
- Contains EPIYA-A, EPIYA-B, and one or more EPIYA-C motifs.
- This type is commonly found in Western populations.
- It has a relatively lower oncogenic potential compared to the East Asian type.
- East Asian-type CagA:
- Contains EPIYA-A, EPIYA-B, and EPIYA-D motifs.
- Predominantly found in East Asian populations.
- This type is associated with a higher risk of gastric cancer due to its stronger interaction with host cellular pathways, leading to more pronounced pathogenic effects.
- In addition to these main types, some more minor types have also been reported:
- Hybrid CagA Types: These strains include a mix of EPIYA motifs, such as both EPIYA-C and EPIYA-D. They may emerge in regions where H. pylori strains from diverse populations coexist.
- Rare Variants: Some strains exhibit unusual arrangements of EPIYA motifs or novel motifs. These are less common and not as well-characterized, but they point to the genetic diversity and adaptability of H. pylori.
- The structural differences in these motifs influence how the CagA protein interacts with host signaling pathways, such as the SHP-2 phosphatase, which plays a role in cellular processes like proliferation and migration. The East Asian-type CagA, with its EPIYA-D motif, has a stronger binding affinity to SHP-2, contributing to its higher oncogenic potential.
