RESUMO
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-1ß 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-1ßrs1143627 were related to UC but not to SCRC.
Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Metilação de DNA , Proteínas Adaptadoras de Transdução de Sinal/genética , Estudos de Casos e Controles , Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Ciclo-Oxigenase 2/genética , Epigênese Genética , Humanos , Interleucina-1beta/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina/genéticaRESUMO
Aim: To investigate the methylation status and single nucleotide polymorphisms (SNPs) of cancer-associated genes in ulcerative colitis (UC) patients and explore the potential mechanism for high cancer risk of UC. Methods: A total of 103 patients were enrolled in our study, which included 30 healthy subjects, 41 patients with early-stage UC, and 32 patients with colorectal cancer (CRC). Methylation status of cyclooxygenase 2 (COX2) and human RUNT-related transcription factor 3 (RUNX3) genes in colonic mucosa from 3 groups of subjects were detected by methylation-specific polymerase chain reaction (PCR). The SNPs TNF-α rs1800629 and IL-1 rs1143627 were genotyped by PCR and direct sequencing. Results: The methylation rate of RUNX3 gene within CRC group was 35.7%, which was significantly higher than the other two groups (Healthy control 5.9%, UC 15.4%, p = .040). There was no significant difference in the methylation rate of RUNX3 between early-stage UC group and healthy control group (p = .633). The methylation rate of COX2 gene, the genotypes (GG, AG) and alleles (A, G) of rs1800629, and the genotypes (CC,CT,TT) and alleles (C,T) of rs1143627 were not statistically different among three groups. Conclusion: In the early stage of UC, the methylation rate of cancer-related genes RUNX3 and COX2 and SNPs TNF-α rs1800629 and IL-1 rs1143627 were not significantly different compared with healthy subjects. The methylation rate of RUNX3 in CRC increased, while the methylation rate of COX2 and SNPs TNF-α rs1800629 and IL-1 rs1143627 did not change significantly compared with the other two groups.
Assuntos
Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Ciclo-Oxigenase 2/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , China , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Metilação de DNA , Feminino , Predisposição Genética para Doença , Humanos , Interleucina-1/genética , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fator de Necrose Tumoral alfa/genéticaRESUMO
AIM: To explore the anti-inflammatory mechanism of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis induced by acetic acid. METHODS: Spragur-Dawley female rats were divided into four groups: Diammonium Glycyrrhizinate group, dexamethasone group, acetic acid control and normal control group. Colonic inflammation was evaluated by disease activity index, gross morphologic damage, histological injury and colonic myeloperoxidase activity. Immunohistochemistry was used to detect the expression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa. RESULTS: Compared to the acetic acid control, both Diammonium Glycyrrhizinate and dexamethasone showed a significant anti-inflammatory effect (P < 0.01). The expression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa was significantly lower in the Diammonium Glycyrrhizinate group and dexamethasone group than in the acetic acid group. CONCLUSION: Diammonium Glycyrrhizinate could reduce inflammatory injury in a rat model of ulcerative colitis. This may occur via suppression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa.
