Impact of catechol-O-methyltransferase (COMT) gene polymorphism on promoter methylation status in gastric mucosa.
DNA methylation is one of the major events in the early process of gastric carcinogenesis and also occurs in non-neoplastic gastric mucosa. Catechol-O-methyltransferase (COMT) catalyzes the methylation of various endobiotic and xenobiotic substances, and protects DNA from oxidative damage. The association between a common functional polymorphism of COMT Val158Met and DNA methylation status in the stomach was investigated.


METHODS
One hundred and sixty-nine gastric mucosa samples from non-cancer patients were obtained by endoscopy. The promoter methylation status of p14 and p16 was determined by methylation-specific PCR (MSP). The COMT Val158Met polymorphism was detected by PCR-restriction fragment length polymorphism (RFLP).


RESULTS
CpG island methylation was observed in 32.5% of the p14, and 37.9% of the p16. The methylation status of both p14 and p16 was not associated with gender or age, while p16 methylation was strongly associated with Helicobacter pylori infection (OR=4.71, 95% CI=2.35-9.46, p<0.0001). The Val/Val genotype held a significantly higher risk of p16 methylation (OR=3.27, 95% CI=1.05-10.25, p=0.0418).


CONCLUSIONS
The COMT polymorphism may influence the susceptibility to gene methylation in the gastric mucosa. The promoter CpG island of p16 gene, but not of p14 may be one of the specific regions whose methylation is closely influenced by the COMT polymorphism.
Tahara
Tomomitsu
T
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. tomomiccyu@yahoo.co.jp
Shibata
Tomoyuki
T
Arisawa
Tomiyasu
T
Nakamura
Masakatsu
M
Yamashita
Hiromi
H
Yoshioka
Daisuke
D
Okubo
Masaaki
M
Maruyama
Naoko
N
Kamano
Toshiaki
T
Kamiya
Yoshio
Y
Fujita
Hiroshi
H
Nagasaka
Mitsuo
M
Iwata
Masami
M
Takahama
Kazuya
K
Watanabe
Makoto
M
Hirata
Ichiro
I
D001483:Base Sequence; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D019175:DNA Methylation; D017931:DNA Primers; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D017931:DNA Primers; D002394:Catechol O-Methyltransferase