The signature of HBV-related liver disease in peripheral blood mononuclear cell DNA methylation.

Clinical Epigenetics
Kang LiYonghong Zhang

Abstract

Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory response. The association between aberrant peripheral blood mononuclear cell (PBMC) DNA methylation and progression of liver disease and fibrosis remains unclear. Here we applied Infinium 450 K BeadChip investigating PBMC genome-wide methylation profiling of 48 HBV-related liver disease patients including 24 chronic hepatitis B (CHB), 14 compensated liver cirrhosis (LC), and 10 decompensated liver cirrhosis (DLC). In total, there were 7888 differentially methylated CpG sites (36.06% hypermethylation, 63.94% hypomethylation) correlate with liver disease progression. LC was difficult to be diagnosed, intermediating between CHB and DLC. We used least absolute shrinkage and selection operator (LASSO)-logistic regression method to perform a LC predictive model. The predicted probability (P) of having LC was estimated by the combined model: P = 1/(1 - e-x), where X = 11.52 - 2.82 × (if AST within the normal range - 0.19 × (percent methylation of cg05650055) - 0.21 × (percent methylation of cg17149911 ). Pyrosequencing validation and confusion matrix analysis was used for internal testing, area under receiver operating characteristic ...Continue Reading

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Methods Mentioned

BETA
biopsy
chip
methylation profiling
density gradient centrifugation
biopsies
Assay
PCR
electrophoresis

Software Mentioned

PyroMarkQ24
stats
package
ChAMP
Ingenuity Pathway Analysis ( IPA
ChAMP Bioconductor
IPA
glmnet R package
R
Bioconductor package

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