MTHFR 677T carrier influences the methylation status of H. pylori-infected gastric mucosa in older subjects.
DNA methylation is one of the major events in the early process of gastric carcinogenesis and it also occurs in non-neoplastic gastric mucosa. MTHFR plays a central role in biotransformation of folate to form S-adenosylmethionine, the universal methyl donor in cells and affects DNA methylation status. We investigated the association between common functional polymorphism of MTHFR C677T and DNA methylation status in H. pylori-infected non-neoplastic gastric mucosa. For 99 gastric mucosa samples from H. pylori positive non-cancer subjects, we assessed the association between MTHFR C677T genetic polymorphism and promoter methylation status of the four candidate promoters (p14, p16, DAP-kinase, and CDH1). In most all of the subjects, weak correlation was found between the p16 promoter methylation and MTHFR 677T carriers (age, sex-adjusted OR = 2.57, P = 0.053). When subjects were divided into two groups according to age, the MTHFR T carrier held a significantly higher risk of p16 promoter methylation, especially in 66 years or older generation (sex-adjusted OR = 14.28, P = 0.02). In addition, mean number of methylated CpG cites were significantly higher in T carrier than CC genotype in the same generation (P = 0.0418). Our data suggest that MTHFR 677T carrier influences the risk of DNA methylation in gastric mucosa in the long-term outcome of the H. pylori infection.
Tahara
Tomomitsu
T
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. tomomiccyu@yahoo.co.jp
Shibata
Tomoyuki
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
Nakagawa
Yoshihito
Y
Nagasaka
Mitsuo
M
Iwata
Masami
M
Takahama
Kazuya
K
Watanabe
Makoto
M
Hirata
Ichiro
I
Arisawa
Tomiyasu
T
D000368:Aged; D000375:Aging / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases