Profiling of cell-free DNA methylation and histone signatures in pediatric NAFLD: A pilot study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652079%3A_____%2F22%3A00567478" target="_blank" >RIV/86652079:_____/22:00567478 - isvavai.cz</a>

Alternative codes found

RIV/00159816:_____/22:00077715

Result on the web

<a href="https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep4.2082" target="_blank" >https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep4.2082</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/hep4.2082" target="_blank" >10.1002/hep4.2082</a>

Result language

angličtina

Original language name

Profiling of cell-free DNA methylation and histone signatures in pediatric NAFLD: A pilot study

Original language description

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and adolescents, increasing the risk of its progression toward nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. There is an urgent need for noninvasive early diagnostic and prognostic tools such as epigenetic marks (epimarks), which would replace liver biopsy in the future. We used plasma samples from 67 children with biopsy-proven NAFLD, and as controls we used samples from 20 children negative for steatosis by ultrasound. All patients were genotyped for patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane bound O-acyltransferase domain containing 7 (MBOAT7), and klotho-beta (KLB) gene variants, and data on anthropometric and biochemical parameters were collected. Furthermore, plasma cell-free DNA (cfDNA) methylation was quantified using a commercially available kit, and ImageStream(X) was used for the detection of free circulating histone complexes and variants. We found a significant enrichment of the levels of histone macroH2A1.2 in the plasma of children with NAFLD compared to controls, and a strong correlation between cfDNA methylation levels and NASH. Receiver operating characteristic curve analysis demonstrated that combination of cfDNA methylation, PNPLA3 rs738409 variant, coupled with either high-density lipoprotein cholesterol or alanine aminotransferase levels can strongly predict the progression of pediatric NAFLD to NASH with area under the curve >0.87. Conclusion: Our pilot study combined epimarks and genetic and metabolic markers for a robust risk assessment of NAFLD development and progression in children, offering a promising noninvasive tool for the consistent diagnosis and prognosis of pediatric NAFLD. Further studies are necessary to identify their pathogenic origin and function.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30401 - Health-related biotechnology

Project

<a href="/en/project/EF15_003%2F0000492" target="_blank" >EF15_003/0000492: Unveiling the molecular determinants of agingto design new therapeutics</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Hepatology Communications

ISSN

2471-254X

e-ISSN

2471-254X

Volume of the periodical

6

Issue of the periodical within the volume

12

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

3311-3323

UT code for WoS article

000870328200001

EID of the result in the Scopus database

2-s2.0-85140252258