Genome-wide analysis of DNA methylation in human peripheral leukocytes identifies potential biomarkers of nonalcoholic fatty liver disease

  • Authors:
    • Rui-Nan Zhang
    • Qin Pan
    • Rui-Dan Zheng
    • Yu-Qiang Mi
    • Feng Shen
    • Da Zhou
    • Guang-Yu Chen
    • Chan-Yan Zhu
    • Jian-Gao Fan
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  • Published online on: March 22, 2018     https://doi.org/10.3892/ijmm.2018.3583
  • Pages: 443-452
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Abstract

The aim of the present study was to uncover the role of leukocytic DNA methylation in the evaluation of nonalcoholic fatty liver disease (NAFLD). Patients with biopsy-proven NAFLD (n=35) and normal controls (n=30) were recruited from Chinese Han population. Their DNA methylation in peripheral leukocytes was subjected to genome-wide profiling. The association between differential methylation of CpG sites and NAFLD was further investigated on the basis of histopathological classification, bioinformatics, and pyrosequencing. A panel of 863 differentially methylated CpG sites dominated by global hypomethylation, characterized the NAFLD patients. Hypomethylated CpG sites of Acyl-CoA synthetase long-chain family member 4 (ACSL4) (cg15536552) and carnitine palmitoyltransferase 1C (CPT1C) (cg21604803) associated with the increased risk of NAFLD [cg15536552, odds ratio (OR): 11.44, 95% confidence interval (CI): 1.04‑125.37, P=0.046; cg21604803, OR: 6.57, 95% CI: 1.02-42.15, P=0.047] at cut-off β-values of <3.36 (ACSL4 cg15536552) and <3.54 (CPT1C cg21604803), respectively, after the adjustment of age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistant (HOMA-IR). Their methylation levels also served as biomarkers of NAFLD (ACSL4 cg15536552, AUC: 0.80, 95% CI: 0.62-0.98, P=0.009; CPT1C cg21604803, AUC: 0.78, 95% CI: 0.65-0.91, P=0.001). Pathologically, lowered methylation level (β-values <3.26) of ACSL4 (cg15536552) conferred susceptibility to nonalcoholic steatohepatitis (NASH). Taken together, genome-wide hypomethylation of peripheral leukocytes may differentiate NAFLD patients from normal controls. The leukocytic hypomethylated ACSL4 (cg15536552) was suggested to be a biomarker for the pathological characteristics of NAFLD.
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July-2018
Volume 42 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang R, Pan Q, Zheng R, Mi Y, Shen F, Zhou D, Chen G, Zhu C and Fan J: Genome-wide analysis of DNA methylation in human peripheral leukocytes identifies potential biomarkers of nonalcoholic fatty liver disease. Int J Mol Med 42: 443-452, 2018.
APA
Zhang, R., Pan, Q., Zheng, R., Mi, Y., Shen, F., Zhou, D. ... Fan, J. (2018). Genome-wide analysis of DNA methylation in human peripheral leukocytes identifies potential biomarkers of nonalcoholic fatty liver disease. International Journal of Molecular Medicine, 42, 443-452. https://doi.org/10.3892/ijmm.2018.3583
MLA
Zhang, R., Pan, Q., Zheng, R., Mi, Y., Shen, F., Zhou, D., Chen, G., Zhu, C., Fan, J."Genome-wide analysis of DNA methylation in human peripheral leukocytes identifies potential biomarkers of nonalcoholic fatty liver disease". International Journal of Molecular Medicine 42.1 (2018): 443-452.
Chicago
Zhang, R., Pan, Q., Zheng, R., Mi, Y., Shen, F., Zhou, D., Chen, G., Zhu, C., Fan, J."Genome-wide analysis of DNA methylation in human peripheral leukocytes identifies potential biomarkers of nonalcoholic fatty liver disease". International Journal of Molecular Medicine 42, no. 1 (2018): 443-452. https://doi.org/10.3892/ijmm.2018.3583