Status of Gene Methylation and Polymorphism in Different Courses of Ulcerative Colitis and Their Comparison with Sporadic Colorectal Cancer

Author:

Liu Chen1ORCID,Yuan Zi-Ying2,Yuan Hao3,Wu Ke-Xiang4,Cao Bin3,Ren Ke-Yu3,Cui Ming-Juan3,Liu Jun-Heng3,Chen Hai-Xing1,Pang Yao-Wei1

Affiliation:

1. Departments of School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, China

2. Department of Gastroenterology, Peking University Third Hospital, Haidian District, Beijing, China

3. Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China

4. Department of Electrophysiology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China

Abstract

Abstract Background The objective of this study is to explore the common genetic and epigenetic mechanism of ulcerative colitis (UC) and sporadic colorectal cancer (SCRC) by observing genes methylation level and single nucleotide polymorphisms (SNPs) of different disease courses in UC and SCRC. Methods Two hundred subjects were enrolled, including 40 in the healthy control (HC) group, 50 in the short disease course UC group (SUC), 52 in the long disease course UC group (LUC), and 58 in the SCRC group. Methylation-specific polymerase chain reaction was used to detect the methylation of MINT1 and cyclooxygenase 2 (COX-2) gene. Single nucleotide polymorphisms of interleukin (IL)-23R rs10889677 and IL-1β rs1143627 were detected by Sanger sequencing. Results Compared with HCs (32.5%), methylation level of MINT1 was significantly increased in SCRC (67.2%; P = 0.001) and was a risk factor for CRC (odds ratio, [OR] 4.26). The methylation ratios of COX-2 were 95.0%, 58.0%, 23.1%, and 24.1% in HC, SUC, LUC, and SCRC, respectively, which were negatively correlated with the disease course of UC (r = −0.290). Hypermethylation of COX-2 was a protective factor for SUC (OR, 0.11), LUC (OR, 0.02), and SCRC (OR, 0.03; P < 0.05). Compared with HCs, rs10889677 allele A was a risk factor for SUC and LUC, and rs1143627 allele T was a protective factor for SUC and LUC. Genotype TT was a protective factor for SUC. Conclusion The hypomethylation of COX-2 gene was a common risk factor and epigenetic modification for UC and SCRC, which might be one of the mechanisms through which UC patients were susceptible to CRC. The hypermethylation of MINT1 was a risk factor for SCRC but not for UC; alleles of IL-23Rrs10889677 and IL-1βrs1143627 were related to UC but not to SCRC.

Funder

Health Commission of Shandong Province

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,Immunology and Allergy

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