Hypermethylated promoters of tumor suppressor genes were identified in Crohn’s disease patients

Abstract

Background/Aims: Overwhelming evidence suggests that inflammatory bowel disease (IBD) is caused by a complicated interplay between the multiple genes and abnormal epigenetic regulation in response to environmental factors. It is becoming apparent that epigenetic factors are significantly associated with the development of the disease. DNA methylation remains the most studied epigenetic modification, and hypermethylation of gene promoters is associated with gene silencing.Methods: DNA methylation alterations may contribute to the many complex diseases development by regulating the interplay between external and internal environmental factors and gene transcriptional expression. In this study, we used 15 tumor suppressor genes (TSGs), originally identified in colon cancer, to detect promoter methylation in patients with Crohn’s disease (CD). Methylation specific polymerase chain reaction and bisulfite sequencing analyses were performed to assess methylation level of TSGs in CD patients.Results: We found 6 TSGs (<i>sFRP1, sFRP2, sFRP5, TFPI2, Sox17</i>, and <i>GATA4</i>) are robustly hypermethylated in CD patient samples. Bisulfite sequencing analysis confirmed the methylation levels of the <i>sFRP1, sFRP2, sFRP5, TFPI2, Sox17</i>, and <i>GATA4</i> promoters in the representative CD patient samples.Conclusions: In this study, the promoter hypermethylation of the TSGs observed indicates that CD exhibits specific DNA methylation signatures with potential clinical applications for the noninvasive diagnosis of IBD and the prognosis for patients with IBD.

Evaluating the Clinical Performance of a Dual-Target Stool DNA Test for Colorectal Cancer Detection

“…In addition, the hypermethylated TFPI2 was also found in patients with Crohn disease. 44 These results imply the potential risk of more falsepositive detections when combining TFPI2 and SDC2.…”

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

“…In conclusion, our results showed that SFRP5 inhibits melanin synthesis in melanocytes through the Wnt/β-catenin signaling pathway in vitro and exhibits melanin-inhibiting activity in vivo . As for the possible mechanism of SFRP5 upregulation in vitiligo melanocytes and vitiligo skin lesions, we speculate that it may be regulated by epigenetics, 74 inflammation, 75 and immune-mediated factors. 76 In recent years, epigenetic changes in SFPR5, such as SFRP5 gene methylation have been closely related to the occurrence and development of various tumors.…”

Personalized medicine in inflammatory bowel disease: Perspectives on Asia

“…47 One Korean study identified hypermethylated promoters of tumor suppressor genes (TSGs) in patients with CD, suggesting they may be candidate noninvasive diagnostic markers of IBD. 48…”