Methylation signatures in peripheral blood are associated with marked age acceleration and disease progression in patients with primary sclerosing cholangitis.
ALP, alkaline phosphatase
ALT, alanine aminotransferase
Aging
BMI, body mass index
DNAm, DNA methylation
ELF, enhanced liver fibrosis
FDR, false discovery rate
GGT, gamma-glutamyltransferase
IBD, inflammatory bowel disease
IL, interleukin
LOXL2, lysyl oxidase-like-2
NASH, non-alcoholic steatohepatitis
PSC, primary sclerosing cholangitis
SMA, smooth muscle actin
UDCA, ursodeoxycholic acid
biomarker
inflammatory bowel disease
primary sclerosing cholangitis
prognosis
ursodeoxycholic acid
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
17
10
2019
revised:
08
11
2019
accepted:
14
11
2019
entrez:
11
2
2020
pubmed:
11
2
2020
medline:
11
2
2020
Statut:
epublish
Résumé
A DNA methylation (DNAm) signature derived from 353 CpG sites (the Horvath clock) has been proposed as an epigenetic measure of chronological and biological age. This epigenetic signature is accelerated in diverse tissue types in various disorders, including non-alcoholic steatohepatitis, and is associated with mortality. Here, we assayed whole blood DNAm to explore age acceleration in patients with primary sclerosing cholangitis (PSC). Using the MethylationEPIC BeadChip (850K) array, DNAm signatures in whole blood were analyzed in 36 patients with PSC enrolled in a 96-week trial of simtuzumab (Ishak F0-1, n = 13; F5-6, n = 23). Age acceleration was calculated as the difference between DNAm age and chronological age. Comparisons between patients with high and low age acceleration (≥ Age acceleration was significantly higher in patients with PSC compared to a healthy reference cohort (median, 11.1 years, This analysis of blood DNAm profiles suggests that compared with healthy controls, patients with PSC - particularly those with cirrhosis - exhibit significant acceleration of epigenetic age. Future studies are required to evaluate the prognostic implications and effect of therapies on global methylation patterns and age acceleration in PSC. An epigenetic clock based on DNA methylation has been proposed as a marker of age. In liver diseases such as non-alcoholic steatohepatitis, age acceleration based on this epigenetic clock has been observed. Herein, we show that patients with primary sclerosing cholangitis have marked age acceleration, which is further accentuated by worsening fibrosis. This measure of age acceleration could be a useful marker for prognostication or risk stratification in primary sclerosing cholangitis.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
A DNA methylation (DNAm) signature derived from 353 CpG sites (the Horvath clock) has been proposed as an epigenetic measure of chronological and biological age. This epigenetic signature is accelerated in diverse tissue types in various disorders, including non-alcoholic steatohepatitis, and is associated with mortality. Here, we assayed whole blood DNAm to explore age acceleration in patients with primary sclerosing cholangitis (PSC).
METHODS
METHODS
Using the MethylationEPIC BeadChip (850K) array, DNAm signatures in whole blood were analyzed in 36 patients with PSC enrolled in a 96-week trial of simtuzumab (Ishak F0-1, n = 13; F5-6, n = 23). Age acceleration was calculated as the difference between DNAm age and chronological age. Comparisons between patients with high and low age acceleration (≥
RESULTS
RESULTS
Age acceleration was significantly higher in patients with PSC compared to a healthy reference cohort (median, 11.1 years,
CONCLUSION
CONCLUSIONS
This analysis of blood DNAm profiles suggests that compared with healthy controls, patients with PSC - particularly those with cirrhosis - exhibit significant acceleration of epigenetic age. Future studies are required to evaluate the prognostic implications and effect of therapies on global methylation patterns and age acceleration in PSC.
LAY SUMMARY
BACKGROUND
An epigenetic clock based on DNA methylation has been proposed as a marker of age. In liver diseases such as non-alcoholic steatohepatitis, age acceleration based on this epigenetic clock has been observed. Herein, we show that patients with primary sclerosing cholangitis have marked age acceleration, which is further accentuated by worsening fibrosis. This measure of age acceleration could be a useful marker for prognostication or risk stratification in primary sclerosing cholangitis.
Identifiants
pubmed: 32039401
doi: 10.1016/j.jhepr.2019.11.004
pii: S2589-5559(19)30154-5
pii: 100060
pmc: PMC7005566
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100060Informations de copyright
© 2019 The Authors.
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