Intact Long‐Type dupA as a Marker for Gastroduodenal Diseases in Okinawan Subpopulation, Japan

Abstract

Background Helicobacter pylori dupA can be divided into two types according to the presence or absence of the mutation. In addition, full-sequenced data revealed that dupA has two types with different lengths depend on the presence of approximately 600 bp in the putative 5' region (presence; long-type and absence; short-type), which has not been taken into account in previous studies. Methods A total of 319 strains isolated from Okinawa, the south islands of Japan, were included. The status of dupA and cagA was determined by polymerase chain reaction. The presence of mutations in long-type dupA was determined by DNA sequencing. Results The prevalence of long-type dupA was 26.3% (84/319). Sequence analysis showed that there were only 6 cases (7.1%) with point mutations lead to stop codon among 84 long-type dupA strains studied. Interestingly, intact long-type dupA without frameshift mutation, but not short-type dupA was significantly associated with gastric ulcer and gastric cancer than gastritis (P = 0.001 and P = 0.019, respectively). After adjustment by age, gender and cagA, the presence of intact long-type dupA was significantly associated with gastric ulcer and gastric cancer compared with gastritis (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.55–7.24 and OR = 4.14, 95% CI = 1.23–13.94, respectively). Conclusions Intact long-type dupA is a real virulence marker for severe outcomes in Okinawa, Japan. The previous information gained from PCR-based methods without taking long-type dupA into account must be interpreted with caution.

Helicobacter pylori with the Intact dupA Cluster is more Virulent than the Strains with the Incomplete dupA Cluster

“…The presence of dupA was 38.6 % in this study, which was relatively lower than that reported in South America and US (79.2 and 69.2 %) [8]. Intriguing, dupA in the region revealed an ORF of 2499-bp, which was a kind of conserved, intact and long-type dupA as recently reported [15,17]. Meanwhile, the long-type dupA is confirmed to produce the encoded protein in the study.…”

“…Notably, as one base pair insertion (T or C) appears after the position 1385 in jhp0917 gene, a continuous ORF ''dupA'' was came into being in some clinical H. pylori strains. dupA was polymorphic [7,13], and the intact long-type dupA was reported, which had a longer open reading frame (2499 bp) than that of strain J99 and is a real virulence marker for severe outcomes in Okinawa, Japan [15]. Recently, our research found that most H. pylori strains had the more active East Asian-type cagA, intact cag PAI, virulent vacA genotypes in a littoral region of Northeast China at high risk of gastroduodenal diseases.…”

Comparative Analysis of the Full Genome of Helicobacter pylori Isolate Sahul64 Identifies Genes of High Divergence

“…This may be due the bifurcated nature of its phylogeny and warrants further investigation. More recently, the presence of its adjacent vir genes has been recognized as a more reliable virulence marker in H. pylori (36,72,73). Evidence that the intact dupA cluster was found in a less virulent strain with cagPAI absent and vacA a putative pseudogene has suggested that the particular dupA cluster found in these strains could be a candidate marker for the prediction of related clinical outcomes.…”

Helicobacter Pylori Virulence and Cancer Pathogenesis

“…These data suggest dupA genotypes can also be defined as long type and short types in relation to location of the signal sequence of the N-terminal region. In Okinawa, only the long-type dupA was significantly associated with severe gastroduodenal diseases [79]. It remains unclear whether the short-type dupA produces a functional protein, or even whether long-type dupA without frame shift mutations are functional.…”