Search for new allelic regions within vacA virulence locus of Helicobacter pylori related to gastrointestinal (GI) diseases

Bakhti, Seyedeh Zahra and Latifi- Navid, Saeid and Zahri, Saber (2015) Search for new allelic regions within vacA virulence locus of Helicobacter pylori related to gastrointestinal (GI) diseases. Masters thesis, University of Mohaghegh Ardabili.

Text (جستجوی جایگاه های آللی جدید در لوکوس بیماری زای vacA هلیکوباکترپیلوری در ارتباط با بیماری های گوارشی) Seyedeh Zahra Bakhti.pdf Download (469kB)

Abstract

Helicobacter pylori (H. pylori) is the main cause of gastric cancer (GC) and peptic ulcer disease (PUD). There is a close relationship between H. pylori-specific factors and different gastroduodenal diseases. The vacA and cagA genes are two main determinants of H. pylori that mainly are involved in development of severe clinical outcomes. The aim of present study was to search new allelic polymorphisms in the 3ʹ-end region of H. pylori vacA gene (denoted c1/c2-c2: no deletion) and compare them with the previous polymorphic regions; vacA-s, -m, -i, and -d and also cagA status in relation to gastroduodenal diseases. A total of 217 H. pylori isolates from 114 patients with gastritis, 46 patients with GC and 57 patients with PUD were obtained and genotyped. Histopathological evaluations were also performed. The total frequency of vacA s1 was 85.4%, s2 7.0 %, m1 32.4%, m2 67.6%, i1 47.9%, i2 49.8%, d1 45.1%, d2 54.0%, c1 28.6%, and c2 63.8% and cagA 69.9%. Statistical analysis showed that the vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with the risk of GC (P< 0.05). The vacA i1 and cagA genotypes were also linked to an increased risk of PUD (P< 0.05), while the vacA s-, m-, and d- genotypes were not independently associated to PUD risk. The vacA c1 region genotype remained in the final model when the GC was considered as a dependant factor by the multiple logistic regression analysis. The vacA c1 genotype showed a strong correlation with the age- and sex-adjusted risk for GC, the OR was 38.32 [95% confidence interval (CI), 6.602-222.290, P = 0.00]. This association was independent of and larger than the associations of vacA m-, i-, and d-type or cagA status with GC. We have proposed that the vacA c1 genotype could therefore be the strongest predictor of GC in Iran.

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