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Bariatric surgery yields genetic changes among patients with NAFLD
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Patients with nonalcoholic fatty liver disease who undergo bariatric surgery may experience DNA-altering effects that can reverse their disease symptoms, according to a recent study.
Researchers evaluated snap-frozen liver biopsies collected from 18 normal controls and 18 healthy obese, 12 obese with steatosis and 15 obese with NASH patients. Follow-up biopsies were performed in seven healthy obese patients, 10 with steatosis and six with NASH at 5 to 9 months after participants had undergone bariatric surgery.
Across the groups, 467 CpG loci were methylated differently at a false discovery threshold of q=.05, with the NASH and normal liver samples as the extreme groups in PCA and heatmap analysis. Nine of 294 genes annotated to these CpGs had 5% or more methylation difference between controls and the NASH group and more than 0.2 log2 change to mRNA expression (P<.05 after correction for multiple testing). These genes code for key enzymes for insulin and insulin-like signaling and intermediate metabolism.
Investigators observed a weak but significant inverse correlation in the changes to DNA methylation between NASH samples and controls before and after bariatric surgery in the CpG loci (P=.004). Methylation was partially reversible at the HOBX1, PRKCZ, SLC38A10 and SECTM1 loci.
Paired analysis before and after surgery indicated 113 sites with different methylation (q=.05), with strong correlations observed between the differences in the control and NASH groups and bariatric surgery (P<2.2 x 10–16). Among the sites, 80 were mapped to 32 gene loci, and researchers noted differential expression of the gene encoding protein-tyrosine phosphatase epsilon before and post-surgery.
Binding sites for TFs GRP20 (P<3.8 x 10–233), SREBP2 (P<3.8 x 10–272), PGC1A (P<1 x 10–300) and ZNF274(P<1 x 10–300) were significantly enriched in the phenotype and bariatric remodeling groups.
“While the presented study is limited … it represents a genome-wide assessment of CpG methylation in NAFLD and its dynamic change induced by the weight loss after bariatric surgery,” the researchers concluded. “Some of the candidate epigenetic driver genes may represent attractive targets for future mechanistic studies and therapeutic inventions.”
Disclosure: See the study for a full list of relevant financial disclosures.
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