Background: Hepatocellular carcinoma (HCC) is the sixth-most common malignancy worldwide. Multiple previous studies have assessed the relationship between TM6SF2 gene polymorphism and the risk of developing HCC, with discrepant conclusions reached. To assess the association of TM6SF2 rs58542926 T/C gene polymorphism with liver cancer, we performed the current meta-analysis. Methods: This study queried the MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to April 2019. Case-control studies assessing the relationship between TM6SF2 rs5854292 locus polymorphism and liver cancer were selected according to inclusion and exclusion criteria. The Stata 12.0 software was employed for data analysis. Results: A total of 5 articles, encompassing 6873 patients, met inclusion criteria and were included in the meta-analysis. Statistical analysis showed that the TM6SF2 gene polymorphism was significantly associated with liver cancer in the allele contrast, dominant, recessive and over dominant models (T vs C, OR = 1.621, 95%CI 1.379–1.905; CT + TT vs CC. OR = 1.541, 95%CI 1.351–1.758; TT vs CT + CC, OR = 2.897, 95%CI 1.690–4.966; CC + TT vs TC, OR = 0.693, 95%CI 0.576–0.834). The Egger’s test revealed no significant publication bias. Conclusion: The present findings suggest a significant association of TM6SF2 gene polymorphism with HCC risk in the entire population studied.

The scaffold protein synectin plays a critical role in the trafficking and regulation of membrane receptor pathways. As platelet-derived growth factor receptor (PDGFR) is essential for hepatic stellate cell (HSC) activation and liver fibrosis, we sought to determine the role of synectin on the PDGFR pathway and development of liver fibrosis. Mice with deletion of synectin from HSC were found to be protected from liver fibrosis. mRNA sequencing revealed that knockdown of synectin in HSC demonstrated reductions in the fibrosis pathway of genes, including PDGFR-β. Chromatin IP assay of the PDGFR-β promoter upon synectin knockdown revealed a pattern of histone marks associated with decreased transcription, dependent on p300 histone acetyltransferase. Synectin knockdown was found to downregulate PDGFR-α protein levels, as well, but through an alternative mechanism: protection from autophagic degradation. Site-directed mutagenesis revealed that ubiquitination of specific PDGFR-α lysine residues was responsible for its autophagic degradation. Furthermore, functional studies showed decreased PDGF-dependent migration and proliferation of HSC after synectin knockdown. Finally, human cirrhotic livers demonstrated increased synectin protein levels. This work provides insight into differential transcriptional and posttranslational mechanisms of synectin regulation of PDGFRs, which are critical to fibrogenesis.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Current studies have shown that PNPLA3 (Patatin-like phospholipase domain containing 3) rs738409 G/C gene polymorphism is associated with adult nonalcoholic fatty liver disease [1, 2].But there is no consensus on the relationship between PNPLA3 rs738409 G/C gene polymorphism and children NAFLD due to differences in population samples. To this end, a meta-analysis of published research is conducted to comprehensively assess the relationship between PNPLA3 gene polymorphism and NAFLD in children. Methods: We searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children’s NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. The Stata 12.0 software was employed for data analysis. Results: A total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children’s NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR = 3.343, 95% CI = 1.524–7.334; GG + GC vs CC,OR = 3.157, 95% CI = 1.446–6.892;GG vs GC + CC,OR = 5.692, 95% CI = 1.941–16.689; GG + CC vs GC,OR = 2.756, 95% CI = 1.729–4.392). Four case-control studies compared Children with nonalcoholic fatty liver (NAFL) and children with nonalcoholic steatohepatitis (NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model (GG vs GC + CC,OR = 14.43, 95% CI = 5.985–34.997); The Egger’s test revealed no significant publication bias. Conclusions: Meta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children.

Background: To assess the association of HSD17B13 rs72613567:TA allelic variant with liver disease, we performed the current review and meta-analysis.Methods: Seven studies were identified by a search of CNKI,CBM,MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to November 2021. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The Stata 14.0 software was employed for data analysis.Results: Statistical analysis showed that the HSD17B13 rs72613567:TA allelic variant can decrease the risk of hepatocellular carcinoma(HCC) in nonalcoholic fatty liver disease (NAFLD) patients, alcoholic fatty liver disease (ALD) patients and viral hepatitis patients (TA vs T OR = 0.766, 95% CI = 0.682–0.860, P = 0.000; TATA + TAT vs TT OR = 0.755, 95% CI = 0.645–0.885, P = 0.001) or healthy controls(TA vs T OR = 0.649, 95% CI = 0.431–0.977, P = 0.038). Besides, the HSD17B13 rs72613567:TA allelic variant can also provide protection from nonalcoholic fatty liver disease (NAFLD) not only in entire population (TA vs T OR = 0.669, 95% CI = 0.524–0.856, P = 0.001) but also in healthy people (TA vs T OR = 0.600, 95% CI = 0.464–0.777, P = 0.000). No significant publication bias found in this airticle.Conclusion: The present findings suggest HSD17B13 rs72613567:TA allelic variant can reduce the risk of HCC and NAFLD in the entire population studied.