title: Influence of IL17A polymorphisms on the aberrant methylation of DAPK and CDH1 in non-cancerous gastric mucosa.
abstract: BACKGROUND
  CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of IL-17 in inflammatory response to H. pylori colonization has been indicated. We investigated the influence of IL17A polymorphisms, -197 G > A (rs2275913) and *1249 C > T (rs3748067), on the methylation of DAPK and CDH1.
  
  
  METHODS
  Gastric mucosal samples were obtained from 401 subjects without malignancies. Methylation status of gene was determined by MSP. The genotyping of IL17A was performed by PCR-SSCP.
  
  
  RESULTS
  Methylations of DAPK and CDH1 were seen in 196 and 149 of all 401 subjects, respectively. Overall, *1249 T carrier was associated with a decreased risk for DAPK methylation, whereas -197 G > A was not. In the subjects older than 60 years old, *1249 T carrier was more strongly associated with gene methylation and -197 A carrier tended to be associated with an increased risk for CDH1 methylation. When evaluating by inflammation promoting haplotype (-197 mutant carrier with *1249 homozygote), this haplotype had a more strongly increased risk for both DAPK and CDH1 methylations in comparatively older subjects. Both atrophy and metaplasia scores were significantly increased with age in -197 A carrier or *1249 CC homozygote, whereas were not in -197 GG homozygote or *1249 T carrier. PG I/II ratio was more significantly decreased in -197 A carrier than in GG homozygote under influence of H. pylori infection.
  
  
  CONCLUSIONS
  In -197 A allele carrier with *1249 CC homozygote, the methylations of both DAPK and CDH1 may be increased gradually, but more rapidly than the other genotypes, with age and altered gastric mucosal structure induced by H. pylori infection.
authors: Department of Gastroenterology, Kanazawa Medical University, Daigaku, Uchinada-machi, Ishikawa, Japan. tarisawa@kanazawa-med.ac.jp
authors: Tomiyasu
authors: T
authors: Arisawa
authors: Tomomitsu
authors: T
authors: Tahara
authors: Mikihiro
authors: M
authors: Tsutsumi
authors: Tomoyuki
authors: T
authors: Shibata
mesh_terms: D000368:Aged; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D002908:Chronic Disease; D019175:DNA Methylation / Q000235:genetics*; D064550:Death-Associated Protein Kinases; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D005756:Gastritis / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery; D006239:Haplotypes; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C513384:CDH1 protein, human; D015820:Cadherins; C508717:IL17A protein, human; D020381:Interleukin-17; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases