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.

Four linked SNPs of PNPLA3 (rs738409, rs3747206, rs4823173, and rs2072906) are correlated with susceptibility to NAFLD, NASH, liver fibrosis, and HBV dynamics in CHB patients.

The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population.

Lung cancer has become the leading cause of cancer-related deaths around the world. In addition to genetic risk factors and smoking, the metabolic risk factors remain to be elusive.To evaluate the associations between obesity, nonalcoholic fatty liver disease (NAFLD) and pulmonary adenocarcinoma in patients with lung cancer.Consecutive operation-proven lung cancer patients with assessment of metabolic disorders and liver ultrasound in 2009 and 2013 were retrospectively enrolled. T-test and multivariate logistic regression were applied to evaluate the contribution of individual factors to lung adenocarcinoma, as well as the synergistic effects between these factors.Among 3664 lung cancer patients with ultrasound examination, 2844 cases were enrolled for further analysis. Of them, 1053 (37.0%) were females, 1242 (43.7%) were cigarette smokers, 1658 (58.3%) were diagnosed as lung adenocarcinoma, 744 (26.2%) had obesity, and 614 (21.6%) had NAFLD. Proportion of female gender, nonsmoker, obesity, NAFLD, and serum lipid levels in patients with adenocarcinoma were significantly higher than those in other subtypes of lung cancer, and in 2013 than in 2009 (all P < .01). NAFLD and obesity were shown as independent factors and positively associated with pulmonary adenocarcinoma, along with female gender and nonsmoking, higher serum levels of cholesterol. NAFLD and other contributing factors exhibited no synergistic effects on adenocarcinoma.Obesity and NAFLD might increase the risk for pulmonary adenocarcinoma, especially in nonsmoking females, and underscore the need for further study into carcinogenic mechanisms and preventive interventions.