Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis.
BACKGROUND
Promoter hypermethylation of tumor suppressor genes is one of the major events in gastric carcinogenesis. Promoter hypermethylation is also present in non-neoplastic gastric epithelium as age-related phenomenon and some reports suggest the potential association between promoter hypermethylation and Helicobacter pylori infection. Here, we examined whether methylation of multiple promoter CpG islands would occur by H. pylori infection and correlate with histological or serological severity of chronic gastritis.


METHODS
One hundred and ninety-one gastric mucosa samples were obtained by endoscopy. The promoter methylation status of the p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific-polymerase chain reaction. The degree of gastritis in the antrum was assessed according to the updated Sydney system in 150 participants. The pepsinogen (PG) I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay in 54 selected cases.


RESULTS
CpG island methylation was found in 32.5% for p14, 35.1% for p16, 43.5% for DAP-kinase and 36.1% for CDH1, whereas non, 1, 2, 3, and all methylation of four promoter CpG sites were present in 46 (24.1%), 59 (30.9%), 46 (24.1%), 30 (15.7%), and 10 (5.2%) participants, respectively. A strong association between the increased number of methylated CpG islands and H. pylori infection was observed (P<0.0001). An increased number of methylated CpG islands was also associated with severity of neutrophil infiltration (P<0.0001), mononuclear cell infiltration (P<0.0001) and atrophy (P=0.0021) in all, and severity of neutrophil infiltration (P=0.0177) and mononuclear cell infiltration (P=0.0004) in H. pylori-positive participants. An increased number of methylated CpG islands correlated with lower PG I/II ratio in all (P=0.0105) and H. pylori-infected participants (P=0.074).


CONCLUSIONS
Multiple promoter CpG islands would be methylated by H. pylori infection, and an increased number of methylated CpG sites correlate with histological and serological severity of chronic gastritis.
Tahara
Tomomitsu
T
Department of Gastroenterology, Kanazawa Medical University, Uchinadamachi, Kanazawa, Ishikawa, Japan. tomomiccyu@yahoo.co.jp
Arisawa
Tomiyasu
T
Shibata
Tomoyuki
T
Nakamura
Masakatsu
M
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
Yamashita
Hiromi
H
Hirata
Ichiro
I
D000368:Aged; D002908:Chronic Disease; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005756:Gastritis / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index