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Background   CDKN2A  hypermethylation is among the major events associated with carcinogenesis and is also observed in non-neoplastic colonic mucosa in patients with ulcerative colitis (UC). Macrophage migration inhibitory factor (MIF) plays a crucial role in promoting gastrointestinal inflammation characteristic of UC. The aim of this study is to explore associations between  CDKN2A  methylation status and  MIF  polymorphisms (rs755622 and rs5844572).    Methods  One hundred and fifty-nine patients diagnosed with UC were enrolled in this study. The methylation status of  p14   ARF   and  p16   INK4a   was determined by MSP;  MIF  genotypes were identified by PCR-SSCP.    Results  We found no differences with respect to mean age, gender, clinical type (chronic continuous or relapse/remitting), or extent of disease among the patients with methylated and unmethylated  p14   ARF   or  p16   INK4a  . Carrying the rs755622 C allele indicated a significantly higher risk for  p14   ARF   methylation (odds ratio (OR), 2.16; 95% confidence interval (CI), 1.08–4.32;  p  = 0.030); similarly, carrying the rs5844572 7-repeat allele indicated a significantly higher risk for  p16   INK4a   methylation (OR, 2.57; 95% CI, 1.26–5.24;  p  = 0.0094) after an adjusted regression analysis. The carriers of the rs755662 C allele or the rs5844572 7-repeat allele were both at a significantly higher risk for methylation of both  p14   ARF   and  p16   INK4a   when compared to the cohort in which neither of the genes were methylated (OR, 2.70; 95% CI, 1.22–6.01;  p  = 0.015 and OR, 2.87; 95% CI, 1.25–6.62;  p  = 0.013, respectively). Additionally, carrying rs755622 C allele was significantly associated with CIHM in chronic continuous of clinical type and total colitis (OR, 25.9; 95% CI, 2.55–262.6;  p  = 0.0059 and OR, 4.38; 95% CI, 1.12–17.2;  p  = 0.034, respectively), and carrying 7-repeat allele of rs5844572 was significantly associated in chronic continuous type (OR, 14.5; 95%CI, 1.46–144.3;  p  = 0.022).    Conclusions  Taken together, our findings suggest that  MIF  genotypes associated with inflammation may also be involved in promoting carcinogenesis via  CDKN2A  hypermethylation in patients diagnosed with UC.

Influence of MIF polymorphisms on CpG island hyper-methylation of CDKN2A in the patients with ulcerative colitis