Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa

Tomomitsu Tahara, Tomoyuki Shibata, Masakatsu Nakamura, Hiromi Yamashita, Daisuke Yoshioka, Masaaki Okubo, Joh Yonemura, Yoshiteru Maeda, Naoko Maruyama, Toshiaki Kamano, Yoshio Kamiya, Hiroshi Fujita, Yoshihito Nakagawa, Mitsuo Nagasaka, Masami Iwata, Ichiro Hirata, Tomiyasu Arisawa

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14 Citations (Scopus)


CpG island hyper-methylation (CIHM) is one of the major events in the gastric carcinogenesis and also occurs in non-neoplastic gastric mucosa. IL-17A, -17F and MIF have a crucial role in the gastric inflammationand carcinogenesis. The CIHM status in the non-cancerous gastric mucosa, in relation to IL-17A (-197G>A, rs2275913), -17F (7488T>C, rs763780) and MIF (-173G>C and -794 tetranucleotide repeats) polymorphisms was investigated. Gastric mucosa samples were obtained from 121 cancer free subjects. CIHM of p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific polymerase chain reaction (MSP). CIHM high was defined as three or all CpG islands methylated. We employed the PCR-SSCP (multiplex PCR for IL-17A and -17F) method to detect the gene polymorphisms. No association were found between CIHM status and L-17A (-197G>A), IL-17F (7488T>C) and MIF (-173G>C) polymorphisms. MIF 5-CATT repeat carrier (5/5+5/6+5/7) held a significantly higher risk of CIHM of DAP-kinase (OR=2.33, 95% CI=1.07-5.09, p=0.03) and CIHM high (OR=3.63, 95% CI=1.31-10.08, p=0.01). Weak association was also found between the same genotype and increased risk of CIHM of p16 (OR=2.45, 95% CI=0.90-6.68, p=0.08) and CDH1 (OR=2.23, 95% CI=0.94-5.32, p=0.07). 6-CATT repeat carrier (5/6+6/6+6/7) was significantly associated with reduced risk of CIHM of p16 (OR=0.31, 95% CI=0.11-0.90, p=0.03), CDH1 (OR=0.40, 95% CI=0.17-0.98, p=0.045), DAP-kinase (OR=0.37, 95% CI=0.17-0.83, p=0.02) and CIHM high (OR=0.25, 95% CI=0.09-0.74, p=0.01). -7-CATT repeat carrier (6/7+7/7) was weakly associated with reduced risk of CIHM of p16 (OR=0.34, 95% CI=0.10-1.13, p=0.08), DAP-kinase (OR=0.43, 95% CI=0.17-1.06, p=0.07) and CIHM high (OR=0.38, 95% CI=0.12-1.20, p=0.098). The present results provided the first evidence that the genetic polymorphisms MIF polymorphism is associated with CIHM status in the human gastric mucosa. Genetic polymorphisms of MIF-794-CATT repeat may be involved in methylation related carcinogenesis in the stomach.

Original languageEnglish
Pages (from-to)563-569
Number of pages7
JournalInternational journal of molecular medicine
Issue number4
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Genetics


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