TY - JOUR
T1 - Influence of MIF polymorphisms on CpG island hyper-methylation of CDKN2A in the patients with ulcerative colitis
AU - Sakurai, Naoko
AU - Shibata, Tomoyuki
AU - Nakamura, Masakatsu
AU - Takano, Hikaru
AU - Hayashi, Tasuku
AU - Ota, Masafumi
AU - Nomura-Horita, Tomoe
AU - Hayashi, Ranji
AU - Shimasaki, Takeo
AU - Ostuka, Toshimi
AU - Tahara, Tomomitsu
AU - Arisawa, Tomiyasu
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/10/12
Y1 - 2020/10/12
N2 - 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.
AB - 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.
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U2 - 10.1186/s12881-020-01140-9
DO - 10.1186/s12881-020-01140-9
M3 - Article
C2 - 33046033
AN - SCOPUS:85092577952
SN - 1471-2350
VL - 21
JO - BMC Medical Genetics
JF - BMC Medical Genetics
IS - 1
M1 - 201
ER -