The prevalence of the duodenal ulcer promoting gene (dupA) in Helicobacter pylori isolates varies by ethnic group and is not universally associated with disease development: a case-control study

<p>Abstract</p> <p>Background</p> <p>The putative <it>H. pylori </it>pathogenicity-associated factor <it>dupA </it>has been associated with IL-8 induction <it>in vitro</it>, and duodenal ulcer (DU) and gastric cancer (GC) development in certain populations, but this association is inconsistent between studies. We aimed to investigate <it>dupA </it>prevalence in clinical isolates from Sweden, Australia and from ethnic Chinese, Indians and Malays resident in Malaysia and Singapore and to examine the association with DU and GC. In addition we investigated the sequence diversity between isolates from these diverse groups and compared the level of IL-8 secretion in isolates possessing and lacking <it>dupA</it>.</p> <p>Methods</p> <p>PCR primers were designed to amplify over the C/T insertion denoting a continuous <it>dupA</it>. PCR products from 29 clinical isolates were sequenced and compared with sequences from three additional strains obtained from GenBank. Clinical isolates from 21 Malaysian patients (8 <it>dupA</it>-positive, 14 <it>dupA</it>-negative) were assessed for their ability to induce IL-8 in AGS cells <it>in vitro</it>. Statistical analysis was performed using Fisher's exact test.</p> <p>Results</p> <p>The prevalence of <it>dupA </it>in isolates from Swedish functional dyspepsia (FD) control patients (65%, 13/20) was higher and in isolates from Indian FD patients (7.1%, 3/42) was lower as compared with isolates from Chinese (28.9%, 13/49, P = 0.005, P = 0.025), Malay (35.7%, 5/14, P = 0.16, P = 0.018) and Australian (37.8%, 17/45, P = 0.060, P < 0.001) FD patients. <it>dupA </it>was associated with DU and GC development in Chinese with 62.5% (10/16) and 54.6% (12/22) of isolates possessing <it>dupA </it>respectively as compared with FD controls (28.9%) (P = 0.015, P = 0.032). No significant difference in prevalence of <it>dupA </it>between FD controls, DU (63.6%, 7/11) and GC (61.9%, 13/21) cases (P = 1.000) was observed in the Swedish population. Sequence analysis revealed a pairwise variation of 1.9% and all isolates possessed the C/T insertion. The average IL-8 induction was 1330 pg/mL for <it>dupA</it>-positive isolates and 1378 pg/mL for <it>dupA</it>-negative isolates.</p> <p>Conclusion</p> <p>Although <it>dupA </it>is highly conserved when present, we identified no consistent association between <it>dupA </it>and DU or GC development across the ethnic groups investigated, with the <it>dupA </it>prevalence in control groups varying significantly. Our results would suggest that in the clinical isolates investigated <it>dupA </it>is not associated with IL-8 induction <it>in vitro</it>.</p