Autophagy‐related genes in Helicobacter pylori infection

• Published in: Helicobacter (Cambridge, Mass.) Vol. 22; no. 3
• Main Authors: Tanaka, Shingo, Nagashima, Hiroyuki, Uotani, Takahiro, Graham, David Y., Yamaoka, Yoshio
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2017
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; ATG16L1; ATG5; Autophagy; Bhutan; DNA microarrays; Epithelial cells; Female; Gastric mucosa; Gastric Mucosa - immunology; Gastric Mucosa - pathology; Gene expression; Gene Expression Profiling; Genes; Genetic Predisposition to Disease; Genotypes; Helicobacter Infections - immunology; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - immunology; Humans; In vitro methods and tests; Infections; Male; Maturation; Microarray Analysis; Middle Aged; Phagocytosis; Polymerase chain reaction; Polymorphism, Single Nucleotide; RNA-directed DNA polymerase; single nucleotide polymorphisms; Single-nucleotide polymorphism; Volunteers; Young Adult; autophagy; Helicobacter pylori; single nucleotide polymorphisms; ATG16L1; ATG5
• DOI: 10.1111/hel.12376
• ISSN: 1083-4389

Background In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy‐related genes in H. pylori infection are not yet fully understood. Materials and Methods We analyzed autophagy‐related gene expression in H. pylori‐infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy‐related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection. Results Microarray analysis of 226 autophagy‐related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori‐positive specimens (n=86) were significantly less than those in H. pylori‐negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori‐positive and 77 H. pylori‐negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18‐0.91) relative to the AA/AG genotypes. Conclusions Autophagy‐related gene expression profiling using high‐throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells.