<i><scp>H</scp>elicobacter pylori</i><scp><i>cagA</i></scp> 12‐bp insertion can be a marker for duodenal ulcer in <scp>O</scp>kinawa, <scp>J</scp>apan

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background and Aim</jats:title><jats:p><jats:italic><jats:styled-content style="fixed-case">H</jats:styled-content>elicobacter pylori</jats:italic> <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content> can be classified into mainly two types (<jats:styled-content style="fixed-case">E</jats:styled-content>ast‐<jats:styled-content style="fixed-case">A</jats:styled-content>sian‐type and <jats:styled-content style="fixed-case">W</jats:styled-content>estern‐type <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content>) according to the repeat regions located in the 3′ region. Recent studies showed that the <jats:styled-content style="fixed-case">W</jats:styled-content>estern‐type <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content> in strains from <jats:styled-content style="fixed-case">O</jats:styled-content>kinawa, <jats:styled-content style="fixed-case">J</jats:styled-content>apan formed a different cluster (<jats:styled-content style="fixed-case">J</jats:styled-content>‐<jats:styled-content style="fixed-case">W</jats:styled-content>estern‐type <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content> subtype). It has also been reported that <jats:styled-content style="fixed-case">J</jats:styled-content>‐<jats:styled-content style="fixed-case">W</jats:styled-content>estern‐type <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content> possesses a 12‐bp insertion located in the 5′ region of <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content> sequence.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The prevalence of 12‐bp insertion in <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content> in <jats:styled-content style="fixed-case">O</jats:styled-content>kinawa and the <jats:styled-content style="fixed-case">U</jats:styled-content>nited <jats:styled-content style="fixed-case">S</jats:styled-content>tates (<jats:styled-content style="fixed-case">U</jats:styled-content>.<jats:styled-content style="fixed-case">S</jats:styled-content>.) was examined by <jats:styled-content style="fixed-case">DNA</jats:styled-content> sequencing. The primer pair that can detect the 12‐bp insertion only by polymerase chain reaction was then designed. The prevalence of strains with 12‐bp insertion was examined in 336 strains isolated from <jats:styled-content style="fixed-case">O</jats:styled-content>kinawa by polymerase chain reaction.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In case of <jats:styled-content style="fixed-case">W</jats:styled-content>estern‐type <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content>/<jats:styled-content style="fixed-case"><jats:italic>vacA</jats:italic></jats:styled-content> s1m2 strains, the prevalence of 12‐bp insertion was significantly higher in strains isolated from <jats:styled-content style="fixed-case">O</jats:styled-content>kinawa than that from the <jats:styled-content style="fixed-case">U</jats:styled-content>.<jats:styled-content style="fixed-case">S</jats:styled-content>. (<jats:italic>P</jats:italic> = 0.002). Phylogenetic tree showed that strains with 12‐bp insertion formed two individual clusters within <jats:styled-content style="fixed-case">J</jats:styled-content>‐<jats:styled-content style="fixed-case">W</jats:styled-content>estern‐type <jats:styled-content style="fixed-case"><jats:italic>cagA</jats:italic></jats:styled-content> subtype; one is from <jats:styled-content style="fixed-case">O</jats:styled-content>kinawa and another is from the <jats:styled-content style="fixed-case">U</jats:styled-content>.<jats:styled-content style="fixed-case">S</jats:styled-content>. The designed primer set showed high sensitivity (100%) and specificity (90.8%) in <jats:styled-content style="fixed-case">O</jats:styled-content>kinawa. The 12‐bp insertion was found in 23.7%, 14.3%, 4.2%, and 4.0% of strains with duodenal ulcer (<jats:styled-content style="fixed-case">DU</jats:styled-content>), gastritis, gastric cancer, and gastric ulcer (<jats:styled-content style="fixed-case">GU</jats:styled-content>), respectively (<jats:italic>P</jats:italic> < 0.001 for <jats:styled-content style="fixed-case">DU</jats:styled-content> <jats:italic>vs</jats:italic> <jats:styled-content style="fixed-case">GU</jats:styled-content>) in <jats:styled-content style="fixed-case">O</jats:styled-content>kinawa.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Although the mechanisms are unknown, the presence of 12‐bp insertion was associated with the presence of <jats:styled-content style="fixed-case">DU</jats:styled-content> and might have a suppressive action on <jats:styled-content style="fi ...