DNA Methylation Patterns According to Fatty Liver Index and Longitudinal Changes from the Korean Genome and Epidemiology Study (KoGES).

Young Kyung Ko,Yoonseok Lee,Young-Sun Lee,Jeong-An Gim,Hayeon Kim

doi:10.3390/cimb44030075

Young Kyung Ko, Yoonseok Lee + Show 3 more

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https://doi.org/10.3390/cimb44030075

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Abstract

The role of differentially methylated regions (DMRs) in nonalcoholic fatty liver disease (NAFLD) is unclear. This study aimed to identify the role of DMR in NAFLD development and progression using the Korean Genome and Epidemiology Study (KoGES) cohort. We used laboratory evaluations and Illumina Methylation 450 k DNA methylation microarray data from KoGES. The correlation between fatty liver index (FLI) and genomic CpG sites was analyzed in 322 subjects. Longitudinal changes over 8 years were confirmed in 33 subjects. To identify CpG sites and genes related to FLI, we obtained enrichment terms for 6765 genes. DMRs were identified for both high (n = 128) and low (n = 194) groups on the basis of FLI 30 in 142 men and 180 women. To confirm longitudinal changes in 33 subjects, the ratio of follow-up and baseline investigation values was obtained. Correlations and group comparisons were performed for the 8 year change values. PITPNM3, RXFP3, and THRB were hypermethylated in the increased FLI groups, whereas SLC9A2 and FOXI3 were hypermethylated in the decreased FLI groups. DMRs describing NAFLD were determined, and functions related to inflammation were identified. Factors related to longitudinal changes are suggested, and blood circulation-related functions appear to be important in the management of NAFLD.

Highlights

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has increased to 25% of the general population and is the main cause of chronic liver disease [1–3]
Most patients show a benign clinical course [4], 20–33% of patients progress to nonalcoholic steatohepatitis (NASH) with fibrosis, which can develop to liver cirrhosis and hepatocellular carcinoma [5,6]
NAFLD can be diagnosed when patients have hepatic steatosis confirmed by liver biopsy and imaging studies such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI)

Summary

Introduction

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has increased to 25% of the general population and is the main cause of chronic liver disease [1–3]. Most patients show a benign clinical course [4], 20–33% of patients progress to nonalcoholic steatohepatitis (NASH) with fibrosis, which can develop to liver cirrhosis and hepatocellular carcinoma [5,6]. NAFLD is associated with elevated risk for cancer development and cardiovascular diseases [7–9]. Several factors are associated with the development and progression of NAFLD, including age, sex, genetics, epigenetics, and other metabolic factors [10–12]. The relationship between NAFLD development and progression and genetic and epigenetic factors has not been fully elucidated. Screening of NAFLD patients in the general population is important to identify patients with a high risk of disease progression. NAFLD can be diagnosed when patients have hepatic steatosis confirmed by liver biopsy and imaging studies such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI)

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