Novel virulence factor dupA of Helicobacter pylori as an important risk determinant for disease manifestation: An overview

Table 1 Important finding on dupA of Helicobacter pylori in chronological order

Year	Observation and conclusion	Sample location	Sample size	Techniques used in the study	Proposed name	Ref.
2005	dupA was novel marker associated with increased risk for DU and reduced risk for gastric cancer in East Asia and South America	Japan, Korea, Colombia	500	PCR, southern blot	dupA	Lu et al[23]
2007	Significant association of dupA gene with DU	North India	166	PCR, Dot-blot hybridization, partial sequencing	dupA	Arachchi et al[24]
2007	Presence of dupA significantly associated with GC than DU	Belgium, South Africa, china, North America	258	PCR	dupA	Argent et al[25]
2008	dupA gene was not associated with any diseases outcome	Iran	157	PCR, partial sequencing	dupA	Douraghi et al[30]
2008	dupA was not associated with H. pylori associated diseases in children and adults	Brazil	482	PCR, partial sequencing	dupA	Gomes et al[26]
2008	dupA was associated with peptic ulcer in Iraqi population but not with Iranian population	Iraq and Iran	108	PCR	dupA	Hussein et al[29]
2008	There was no association between the occurrence of dupA and DU	Brazil (Sao Paulo)	79	PCR	dupA	Pacheco et al[27]
2008	The prevalence of dupA was significantly higher in DU patients than in gastric cancer	china	360	PCR	dupA	Zhang et al[38]
2009	There was no consistent association between dupA and DU or GC development	Sweden, Australia, Malaysia (ethnic groups Indian, Malaya)	243	PCR, partial sequencing	dupA	Schmidt et al[41]
2010	dupA was not associated with gastroduodenal diseases or IL-8 production	Japan	244	PCR, partial sequencing RT-PCR, IL-8 assay	dupA	Nguyen et al[45]
2010	dupA is not association with DU in patients from Turkey	Turkey	91	PCR	dupA	Tuncel et al[37]
2010	Meta-analysis of case control studies confirmed the presence of dupA gene for DU	Asian and western countries	2466	-	dupA	Shiota et al[44]
2010	Meta-analysis of previous report showed dupA gene promotes DU formation some population and GU and GC in others	Around the world	2358		dupA	Hussein et al[43]
2010	In Taiwanese female population, MMP-3 promoter polymorphism is correlated with DU rather than dupA gene	Taiwan female	181	PCR	dupA	Yeh et al[40]
2010	dupA and gastric cancer is negatively associated with GC in Japanese population	Japan	136	PCR	dupA	Imagawa et al[46]
2010	Proposed two alleles of dupA [dupA1 (intact), dupA2 (truncated)]. dupA1 (not dupA2) increased IL-12p40 and IL-12p70 production from CD14+ mononuclear cell	United Kingdom, United States, Belgium, South Africa, China	34	PCR, full Sequencing, Cytokine ELISA, real tome PCR, flow cytometry	dupA1	Hussein et al[52]
2011	Presence of mutation on dupA at 1311 and 1426 leads to stop codon called truncated dupA	Brazil	252	PCR, full sequencing	dupA	Queiroz et al[50]
2011	Intact dupA (dupA1) without stop codon was associated with decreases rate of gastric carcinoma in Brazilian population	Brazil	6	Full sequencing	dupA1	Queiroz et al[57]
2012	Found a positive association between presence of dupA and DU [OR 24.2; 95%CI: 10.6-54.8] and inverse association between presence of dupA and GU [OR 0.34; 95%CI: 0.16-0.68] and GC [OR 0.16; 95%CI: 0.05-0.47]	Iran	216	PCR	dupA	Abadi et al[31]
2012	Prevalence of dupA was higher in the eradication failure group than in the success group (36.3% vs 21.9%)	Japan	142	PCR, Drug sensitivity test	dupA	Shiota et al[60]
2012	The logistic analysis report in Brazilian population showed the presence of intact dupA independently associated with duodenal ulcer (OR = 5.06; 95%CI: 1.22-20.96, P = 0.02)	Brazil	75	Sequencing	Intact dupA	Moura et al[51]
2012	dupA gene was found to be significantly associated with DU than in NUD in south east Indian population	India	140	PCR, partial sequencing, real time PCR,	dupA	Alam et al[47]
2012	Found a significant association between dupA1 and DU (P < 0.01) along with a significant higher level of gastric mucosa IL-8 in dupA1 than in dupA2 or dupA negative Iraqi strain	Iran	68	PCR, full sequencing, IL-8 ELISA	dupA1	Hussein et al[54]
2012	classified dupA into two types (long types and short types) depend on the presence of 615 bp at the N-terminal of dupA. Found high prevalence of intact long type dupA (24.5%) than short type dupA (6.6%) and significantly associated with GU and GC than gastritis (P = 0.001 and P = 0.019) in Japanese population	Japan	319	PCR, full sequencing	Long type and short type	Takahashi et al[53]
2012	Complete dupA cluster (dupA with six virB homologues) was associated with DU rather than dupA gene only in United States population	United States	245	PCR and cytokine ELISA	dupA cluster	Jung et al[75]
2013	Prevalence of long type dupA (2499 bp) was significantly higher in GU, GC and DU (40.3%) than from gastritis (20.4%) (P = 0.02) in China	China	116	PCR, Full sequencing	dupA cluster	Wang et al[59]
2013	PUD was significantly associated with cagA (P ≤ 0.017; OR 0.4; 95%CI: 0.18-0.85) rather than dupA	Iraq	154	PCR	dupA	Salih et al[34]
2014	dupA was found to play an important role in the development of DU, BGU and dysplasia in South Korean population	South Korea	401	PCR	dupA	Kim et al[39]
2014	dupA was associated with cagA and vacAs1m1 genotypes	Brazil	205	PCR	dupA	Pereira et al[28]
2014	The prevalence of dupA and cagA were more in MTZ, CLR and AML resistance strain as compared to other virulence factor in Pakistan	Pakistan	46	PCR	dupA	Rasheed et al[61]
2015	cagA, complete dupA cluster and smoking were significantly associated with increased level of IL-8 production from gastric mucosa of Iraqi population	Iraq	81	PCR, IL-8 ELISA	dupA	Hussein et al[55]
2015	Prevalence of dupA1 was significantly higher in DU than NUD (P = 0.02) in Indian strains and dupA1 positive strains were similar to East Asian strains and distinct from western strains.	India	170	PCR, sequencing, IL-8 ELISA	dupA1	Alam et al[58]
2015	Significant association of complete dupA cluster with IL-8 production (P < 0.01) in north East of China	China	262	PCR, western blotting, IL-8 ELISA	dupA cluster	Wang et al[76]
2015	DupA protein have ATPase activity and play a role in apoptosis of gastric cancerous cells through mitochondrial pathway but neither adhere nor translocate to host cell	China	1 (WH21)	PCR, western blotting, ATPase, Adhesion, translocation and cytotoxic assay	Long type dupA	Wang et al[79]
2015	dupA1 have a significant association with A2147G clarithromycin resistance strain but not with Il-8 production from gastric mucosa	Iraq	74	PCR, IL-8 ELISA, antibiotic susceptibility teat	dupA1	Hussein et al[56]
2015	Significant association between the presence of dupA and DU diseases (P = 0.03 OR 3.14, 95%CI: 1.47-7.8).	Iran	128	PCR	dupA	Haddadi et al[35]
2015	There was no significant relationship between dupA status and duodenal ulcer disease (P = 0.25) but, there was a converse relationship between dupA negative strains and gastric cancer disease (P = 0.02)	Iran	123	PCR	dupA	Souod et al[36]
2015	There was no association of dupA gene with the ethnic group (Indian, Chinese, Malaya) of Malaysia	Malaysia	105	PCR	dupA	Osman et al[42]
2017	Significant association of dupA gene with non-severe clinical outcome (P = 0.0032, OR 0.25, 95%CI: 0.09-0.65) and play a role in protecting against gastric cancer in Chile	Chile	132	PCR	dupA	Paredes et al[48]
2017	A complete tfs plasticity zone cluster including dupA is a virulence factor that may be important for the colonization of H. pylori and to the development of severe outcomes of the infection with cagA-positive strains	Portugal	18	PCR, whole genome sequencing, cytokine assay	dupA	Silva et al[78]
2019	dupA was significantly associated with decreased risk of duodenal ulcer (P = 0.024)	Costa Rica	151	PCR	dupA	Molina Castro et al[49]
2019	Significant relationship was observed between the occurrence of DU and the presence of the 112 bp segment (P = 0.002; OR 6.98; 95%CI: 1.94-25.00)	Iran	143	PCR	dupA	Fatahi et al[32]
2019	The prevalence of dupA was 53.4% in South African population, but it was not associated with duodenal ulcer	South Africa	234	PCR	dupA	Idowu et al[64]
2019	The prevalence of dupA was higher (30.4%) in peptic ulcer (mild diseases) than gastric cancer (severe diseases) 18.2%	Northern Spain	102	PCR	dupA	Fernandez-Reyes et al[72]
2019	dupA was present in 10/41 (24.4%) of population, and it was not associated with severe gastritis	Switzerland	41	Whole genome sequence	dupA	Imkamp et al[63]
2019	Significant association was found between metronidazole resistance and dupA genotypes (P = 0.0001)	Iran	68	PCR	dupA	Farzi et al[33]

CI: Confidence interval; DU: Duodenal ulcer; GC: Gastric cancer; GU: Gastric ulcer; IL-8: Interleukin-8; MMP-3: Matrix metalloproteinase -3; NUD: Non-ulcer dyspepsia; OR: Odds ratio; PCR: Polymerase chain reaction.