Significant association between PTPN11 polymorphism and gastric atrophy among Japanese Brazilians.
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.
Kawai
Sayo
S
Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Goto
Yasuyuki
Y
Ito
Lucy S
LS
Oba-Shinjo
Sueli M
SM
Uno
Miyuki
M
Shinjo
Samuel K
SK
Marie
Suely K N
SK
Ishida
Yoshiko
Y
Nishio
Kazuko
K
Naito
Mariko
M
Hamajima
Nobuyuki
N
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
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