Survey of the Clonal Genealogies of Helicobacter pylori cagA Gene in Iran and Their Relationship to Gastrointestinal Diseases

Sheikhbagher, Sanaz (2018) Survey of the Clonal Genealogies of Helicobacter pylori cagA Gene in Iran and Their Relationship to Gastrointestinal Diseases. Masters thesis, University of Mohaghegh Ardabili.

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Abstract

Background & Aims: There is a relationship between cagA gene of Helicobacter pylori genes and the increased risk of clinical outcomes. This gene also possess strong patterns of geographical differentiation. The aim of the present study was to analyze the sequence of the N-terminal and central cagA gene of Helicobacter pylori to determine patterns of genetic diversity and its relation with clinical outcomes. Materials and Methods:656 nucleotides of cagA gene (413 nucleotides: the N-terminal region and 243 nucleotides: central region) in 95 strains of cagA positive from a total of 250 strains of H. pylori isolates from diverse geographical and ethnic sources within Iran, were sequenced and analyzed.We used phylogenetic methods to determine the patterns of nucleotide diversity, and the relationship between evolutionary lineages and clinical status by PCR amplification. Data were collected and analyzed using SPSS version 23. Results: Phylogenetic analyses of Iranian cagA gene disclosed four lineages. The cagA lineage II showed extensive genetic diversity compared with lineage I. cagA lineages III and IV disclosed mixed ancestries with recombinant nucleotides that originated from lineages I and II. cagA lineage II was different from the two Eastern and Western dynasties. In 250 H. pylori isolates recovered from patients with digestive disorders, 128/250 with non-atrophic gastritis (NAG), 59/250 with peptic ulceration (PUs) and 63/250 with gastric cancer (GC). In general, cagA+ genotype could be determined in 157 (62.8%) strains. Of the 157cagA+ strains, 45 (28.7%) had cagA lineage II genotype (NAG: 19.0%, PUs: 36.5%, and GC: 42.3%); and results of simple logistic regression analysis showed a strong correlation between this genotype and risk of GC [OR (95% CI) = 3.129 (1.198-8.171); P = 0.020] and Pus [OR (95% CI) = 2.45 (1.107-5.449); P = 0.027]. In the multiple logistic regression analysis, when the GC was considered as a dependent factor, after adjusting of variables of age and sex, the cagA lineage II genotype remained in the final model (P = 0.038, OR=3.254; 95% CI=1.069-9.903). Conclusion: The increased level of nucleotide diversity in H. pylori cagA gene shows strong evolutionary dynamics, led to the emergence of new clonal lineages in Iranian cagA gene particular cagA lineage II that was linked to GC and PUs diseases.

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