Dataset Information

Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).

ABSTRACT: BACKGROUND:Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. RESULTS:A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. CONCLUSIONS:In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.

SUBMITTER: Buzova D

PROVIDER: S-EPMC7441674 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).

Buzova Diana D Maugeri Andrea A Liguori Antonio A Napodano Cecilia C Lo Re Oriana O Oben Jude J Alisi Anna A Gasbarrini Antonio A Gasbarrini Antonio A Grieco Antonio A Cerveny Jan J Miele Luca L Vinciguerra Manlio M

Clinical epigenetics 20200820 1

<h4>Background</h4>Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity o ...[more]

PMID: 32819448

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Project description:BackgroundAs fat and obesity play a vital role in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD), this study aims to investigate the association between the fat mass and obesity-associated gene (FTO) and MAFLD.MethodsSix SNPs (rs6499640, rs1421085, rs8050136, rs3751812, rs9939609 and rs9930506) within FTO were genotyped for 741 MAFLD patients (median age, 69.98; interquartile range, 66.55-75.93) and 825 healthy people (median age, 69.94; interquartile range, 66.39-75.64). Allele and genotype frequencies, pairwise linkage disequilibrium (LD) and haplotype analysis were calculated.ResultsBMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglyceride, alanine transaminase, glutamyl transpeptidase and the prevalence of diabetes were found to be higher in the MAFLD individuals comparing to the control ones (P < 0.05). For rs1421085, the C allele frequency was remarkably higher in MAFLD after Bonferroni correction (OR [95% CI] =1.353 [1.095-1.671]; P corr =0.030), and a significantly different genotype result was observed in log-additive model (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024). For rs8050136, significantly increased A allele frequency was observed in MAFLD (OR [95% CI] =1.371 [1.109-1.695]; P corr =0.024), and A-allele carriers showed increased MAFLD risk (OR [95% CI] =1.393 [1.103-1.759]; P corr =0.030). For rs3751812, the T allele frequency was remarkably higher in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024), and T-allele carriers demonstrated high MAFLD risk (OR [95% CI] =1.392 [1.103-1.756]; P corr =0.030). For rs9939609, A allele frequency was also remarkably high in MAFLD (OR [95% CI] =1.369 [1.108-1.691]; P corr =0.024), and A-allele carriers were more susceptible to MAFLD (OR [95% CI] =[1.103-1.756]; P corr =0.030). A strong LD was found among rs1421085, rs8050136, rs3751812 and rs9939609 (r2 >0.8), and individuals with C-A-T-A haplotype had an elevated MAFLD risk (P =0.005).ConclusionThe case-control study indicated that C variant of rs1421085, A variant of rs8050136, T variant of rs3751812 and A variant of rs9939609 are associated with elevated MAFLD risk in the older Chinese Han population.

Dataset Information

Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).

Publications

Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).

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