title: Significant association between PTPN11 polymorphism and gastric atrophy among Japanese Brazilians.
abstract: BACKGROUND
  Helicobacter pylori, especially the cytotoxin-associated antigen A (cagA)-positive strains, plays a crucial role in the development of gastric atrophy and gastric cancer. CagA delivered into gastric epithelial cells combines with src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2), possibly leading to atrophy/cancer. Our previous study found that a single-nucleotide polymorphism (SNP; IMS-JST057927) of the PTPN11 gene encoding SHP-2, was associated with gastric atrophy among H. pylori-seropositive subjects. This study aimed to examine the reproducibility of the association among Japanese residing in a different circumstance.
  
  
  METHODS
  The subjects were 918 healthy adult Japanese Brazilians from four different areas in Brazil. Blood was sampled from March to May 2001. The target SNP in intron 3 of PTPN11 was genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Gastric atrophy was evaluated with serum pepsinogens (PGs); PG I, less than 70 ng/dl and PG I/II ratio, less than 3.
  
  
  RESULTS
  The genotype frequency of PTPN11 was in Hardy-Weinberg equilibrium: 65.5% for G/G, 30.4% for G/A, and 4.1% for A/A. The PTPN11 polymorphism had no significant association with H. pylori seropositivity. Among the H. pylori-seropositive subjects, the odds ratios (ORs) of gastric atrophy were 0.93 (95% confidence interval [CI], 0.59-1.47) for the G/A genotype and 0.31 (95% CI, 0.10-0.95) for the A/A genotype, compared with the G/G genotype.
  
  
  CONCLUSIONS
  The present study reproduced the significant association between the A/A genotype and reduced risk of gastric atrophy among Japanese outside Japan. According to the Japan Single Nucleotide Polymorphisms (JSNP) database (db)SNP data, the G allele is very frequent among Japanese and rare in Caucasians. This fact may partly explain the distribution of gastric atrophy/cancer in the world.
authors.affiliation: Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Lucy S
authors.initials: LS
authors.lastname: Ito
authors.forename: Sueli M
authors.initials: SM
authors.lastname: Oba-Shinjo
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uno
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Shinjo
authors.forename: Suely K N
authors.initials: SK
authors.lastname: Marie
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ishida
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nishio
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001938:Brazil; D005260:Female; D005757:Gastritis, Atrophic / Q000235:genetics* / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D018909:src Homology Domains
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases