There are several studies which have shown, that the incidence and / or severity of gastrointestinal diseases related to H. pylori may vary geographically . Further, there are several reports for the presence of different strains of H. pylori with different degree of virulence indicating variation in the distribution of different virulent genes of H. pylori in different populations [17–19]. Several Indian studies show that cagA gene was found at a high frequency of 86% of the H. pylori strains and this virulence marker was found at almost equal frequencies in strains from DU patients (90.6%) and NUD patients (82%), indicating that the prevalence of the cagA gene cannot be considered as a key virulence marker for determination of the clinical status of the host [10, 20]. This is very similar to the results in our present study, where we found the prevalence rate of 79.8% for cag A positivity among H. pylori related gastrointestinal diseases. We found large geographical differences in the prevalence rates in different parts of India. We found that the prevalence of cagA in North India, South India, North-East India were 44.6%, 90% and 93.9% respectively. cagA was significantly associated (p < 0.05) with Gastritis and DU, where its prevalence was 92.5% and 88.3% respectively compared to prevalence rate of 65% (13/20) among controls. On the other hand, the prevalence of cagA gene among GERD, NUD and Gastric Ulcer were 50%, 72.5% and 71.4% respectively but was not significant. Our results are in line with the findings and observations of other studies from India which show a high cagA prevalence among DU and Gastritis patients. Prevalence was also high among NUD and PUD patients but they did not reach significance. The prevalence of cagA phenotype was also lower in patients with GERD as has been the observation of other studies as well .
We also found the overall prevalence rate of 75.2% for the vacAs1m1 allele was highest followed by vacAs2m2 (16.9%) and vacAs1m2 (7.9%). This data is in accordance to previous studies having about 70% s1m1 allele in Indian H. pylori isolates . We found significant association (p < 0.05) of the virulent allele s1m1 with Gastritis and Duodenal Ulcer but not with others viz. GERD, DU and Gastric Ulcer. Our present observations are in line with the other studies from India . Although there is geographical variation in the prevalence of vacAs1m1 with 91.5% in North East India, 90% in South India, 74% in East India. In North India, the prevalence of s1m1 is 40% where as 43% is s2m2 which is similar to reports from Kauser et al 2005 from Ladakh, India where they found that 60% of the strains have s2 genotype .
We for the first time in the world analyzed the prevalence of tipα gene among the H. pylori strains and its association with virulent genes cagA, vacA gene in various gastrointestinal diseases. Our study shows that the overall prevalence of tipα, among the Indian H. pylori isolates is 59.9%. NUD has been to be significantly associated with tipα with a prevalence rate of 86.3% compared to the prevalence of 60% among controls. The prevalence rate were similar to NUD (86.3%) and GERD while the prevalence rates were much lower in Gastritis (41.3%), DU (57.1%) and Gastric Ulcer (42.9%). The highest prevalence rate of tipα gene was found in 95.6% (22/23) vacAs1m2 positive H. pylori strains indicating a strong correlation between them. Another study has also reported increased mucosal IL-18 mRNA expression in vacAs1m2 allele causing increase in the risk of gastro-duodenal disease although no significance was found . It has been found that Gastric Cancer patients infected with tipα positive strains of H. pylori produce significantly higher amounts of TNF-α than patients with chronic Gastritis and that TNF-α induced inflammatory response plays a significant role in the development of Gastritis and Gastric Cancer associated with H. pylori infection .
Our study also demonstrates the significant association of tipα gene with Non Ulcer Dyspepsia (NUD). Non Ulcer Dyspepsia refers to heterogeneous and broad range of chronic upper abdominal symptoms which are widely shared with different gastrointestinal disorders. Therefore, NUD is generally diagnosed when other frequent gastrointestinal diseases are excluded, and upper endoscopy ruled out macroscopic lesions - i.e., Gastritis or Peptic ulcer. Such a condition is frequently encountered in clinical practice, its prevalence being close to 20%-30% in the general population and probably predates the occurrence of Gastritis and PUD. To date, no conclusive data have been reported on the role of H. pylori infection on these dysfunctions. A Cochrane Meta-analysis of 17 trials with 3,566 patients showed that there was a 10% (95% CI: 6–14) relative risk reduction of dyspepsia following H. pylori eradication as compared to placebo, with a NNT of 14 (95% CI: 10–25). H. pylori infection may cause dyspeptic symptoms in NUD through other mechanisms such as: (1) alterations of gastric acid secretion; (2) persistent and active inflammation of gastric mucosa; and (3) post-infective changes in gastroduodenal mucosa. Our study raises a possibility of tipα being the link between H. pylori and NUD. This merits a further larger studies to comprehensively understand this possibility .
In summary, our results revealed, for the first time in the world that the prevalence rate of tipα gene is 59.9% (160 out of 267) among the Indian population. There is a highly significant association between virulent gene cagA and vacAs1m1 alleles with Duodenal Ulcer and Gastritis. We found a significant association of tipα gene with Non Ulcer Dyspepsia (NUD). Further, larger studies will be required to determine the clinical relevance of Tipα as a clinical parameter in NUD and other H. pylori related gastro-intestinal diseases.