DNA methylome analysis reveals epigenetic alteration of complement genes in advanced metabolic dysfunction-associated steatotic liver disease

Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the po...

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Published in:Clinical and molecular hepatology 2024-10, Vol.30 (4), p.824
Main Authors: Amal Magdy, Hee-jin Kim, Hanyong Go, Jun Min Lee, Hyun Ahm Sohn, Keeok Haam, Hyo-jung Jung, Jong-lyul Park, Taekyeong Yoo, Eun-soo Kwon, Dong Hyeon Lee, Murim Choi, Keon Wook Kang, Won Kim, Mirang Kim
Format: Article
Language:Korean
Subjects:
Complement
DNA methylation
Epigenetics
MASH
MASLD
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Summary:Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction-associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (P
ISSN:2287-2728