Distinct cagA EPIYA Motifs are Associated with Ethnic Diversity in Malaysia and Singapore

Abstract

In vitro studies have shown that the biologic activity of CagA is influenced by the number and class of EPIYA motifs present in its variable region as these motifs correspond to the CagA phosphorylation sites. It has been hypothesized that strains possessing specific combinations of these motifs may be responsible for gastric cancer development. This study investigated the prevalence of cagA and the EPIYA motifs with regard to number, class, and patterns in strains from the three major ethnic groups within the Malaysian and Singaporean populations in relation to disease development. Helicobacter pylori isolates from 49 Chinese, 43 Indian, and 14 Malay patients with functional dyspepsia (FD) and 21 gastric cancer (GC) cases were analyzed using polymerase chain reaction for the presence of cagA and the number, type, and pattern of EPIYA motifs. Additionally, the EPIYA motifs of 47 isolates were sequenced. All 126 isolates possessed cagA, with the majority encoding EPIYA-A (97.6%) and all encoding EPIYA-B. However, while the cagA of 93.0% of Indian FD isolates encoded EPIYA-C as the third motif, 91.8% of Chinese FD isolates and 81.7% of Chinese GC isolates encoded EPIYA-D (p < .001). Of Malay FD isolates, 61.5% and 38.5% possessed EPIYA-C and EPIYA-D, respectively. The majority of isolates possessed three EPIYA motifs; however, Indian isolates were significantly more likely to have four or more (p < .05). Although, H. pylori strains with distinct cagA-types are circulating within the primary ethnic groups resident in Malaysia and Singapore, these genotypes appear unassociated with the development of GC in the ethnic Chinese population. The phenomenon of distinct strains circulating within different ethnic groups, in combination with host and certain environmental factors, may help to explain the rates of GC development in Malaysia.