Carcinoma, Hepatocellular ; Humans ; Lipase ; Liver Neoplasms ; Membrane Proteins ; Polymorphism, Genetic

Objective To investigate the association between the Adiponectin rs266729 and rs2241766 gene polymorphisms and nonalcoholic fatty liver disease in the Han Chinese population residing in Qingdao. Methods Adiponectin rs266729 and rs2241766 gene polymorphisms were genotyped in patients with NAFLD (n = 336) and healthy controls (n = 280) using polymerase chain reaction (PCR). Serum lipid profiles and adiponectin levels were determined using biochemical methods. Statistical analyses were performed using Pearson Chi square test, logistic regression analysis, t test, linear regression analysis. Results We found a significant association between the Adiponectin rs266729 genotype frequencies and allele frequencies between NAFLD pa-tients and controls (χ2= 9.929, P = 0.007; χ2= 9.809, P = 0.002). After adjustment of confounding factor, the rs266729 G allele was associated with an increased risk of NAFLD compared to the C allele (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008) No significant differences were found in the rs2241766 genotype frequencies and allele frequencies between NAFLD population and the controls (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008). Conclusion The Han Chinese in Qingdao carrying the rs266729 G allele are at increased risk of NAFLD.

Objective To investigate the association between (beta-parvin) PARVB gene rs5764455 polymorphism and susceptibility to non-alcoholic fatty liver disease (NAFLD). Methods A total of 230 patients with NAFLD (NAFLD, n = 230) and 230 control subjects (control, n = 330) were genotyped by PCR and direct sequencing. Clinical information was detected and compared in different groups. Genotypic frequency and gene frequency distribution in the two groups and relative risks to NAFLD susceptibility were assessed statistically , respectively. Results No statistical differences were observed between PARVB gene rs5764455 genotypic frequency with gene frequency distribution and the two groups, respectively (Genotypic frequency χ2 = 0.182, P = 0.913; gene frequency χ2 = 0.180, P = 0.672). Comparing C/T + T/T genotype carrier with C/C genotype carrier, there were no differences concerning the relative risks to NAFLD susceptibility (OR = 1.266, P =0.178;adjusted OR =1.631, P =0.096) before and after adjusting body mass, BMI and so on. In the latter group, there are significant differences in the increases of body mass, BMI, TG, ALT and AST (P < 0.05). Conclusion Non-relationship was observed between PARVB gene rs5764455 polymorphism and the risk of NAFLD in Qingdao Han Chinese.

Adult ; Female ; Hepatitis B, Chronic ; blood ; pathology ; Humans ; Liver Cirrhosis ; blood ; pathology ; Liver Function Tests ; Male ; Middle Aged ; Transforming Growth Factor beta ; blood ; Transforming Growth Factor beta1

ObjectiveTo investigate the mechanism of action of PNPLA3 I148M mutation in the development and progression of non-alcoholic fatty liver fibrosis. MethodsThe lentiviral vectors carrying the mutant or wild-type PNPLA3 I148M gene were constructed and transfected into rat hepatic stellate (HSC-T6) cells. Quantitative real-time PCR was applied to measure the mRNA expression of transforming growth factor β1 (TGF β1). The t-test was applied for statistical analysis. ResultsThe lentiviral vectors carrying the mutant or wild-type PNPLA3 I148M gene were successfully constructed and transfected into HSC-T6 cells, and a HSC-T6 cell line with stable expression of the mutant or wild-type PNPLA3 gene was established. Compared with the cell line carrying the wild-type gene, the cell line carrying the mutant gene showed significantly higher mRNA expression of TGF β1 (1.25±0.15 vs 0.48±0.07; t=11.826, P＜0001). ConclusionPNPLA3 I148M mutation can increase the expression of TGF β1 in HSC-T6 cells, which provides a new cell model and new research ideas for investigating the role of PNPLA3 I148M mutation in non-alcoholic fatty liver fibrosis.

Transmembrane 6 superfamily member 2 (TM6SF2) is a recently discovered gene,which is located on the chromosome 19 (19p12) and encodes a protein consisting of 351 amino acids.Presently,many studies have reported that the single-nucleotide polymorphism of TM6SF2 rs58542926 and plasma lipids are closely related to the incidence and development of diseases,such as non-alcoholic fatty liver disease (NAFLD),cardiovascular disease (CVD),liver cancer,and hepatitis C.This review will summarize the research progress conducted in these areas.

OBJECTIVETo investigate the relationship between SREBP-1c and the risk of liver disease associated with the triacylglyceride lipase PNPLA3 I148M variant using a human hepatoma cell line model transfected with recombinant lentiviruses.

METHODSHuh7 cells were transfected with control lentivirus or lentivirus containing the PNPLA3 I148M variant (variant). The two cell groups were compared to assess differences in triglyceride content (using oil red O staining), levels of triglyceride and cholesterol (using automated biochemical analyzer), expression of SREBP-lc mRNA (using fluorescence quantitative PCR), and expression of SREBP-1c protein (using western blot.

RESULTSCells expressing the PNPLA3 I148M variant showed higher triglyceride content (0.54+/-0.03 mmol/L vs. control cells: 0.23+/-0.02 mmol/L; t=22.58, P<0.001), cholesterol level (0.28+/-0.03 mmol/L vs. control cells: 0.13+/-0.02 mmol/L; t =11.83, P<0.001), SREBP-1cmRNA expression (13.59+/-0.60 vs. 11.81+/-0.82; [The abstract and text in the paper say variant increases, but the data shown says the higher value is in the control cells. Please correct to properly express the data.] P=0.001), and SREBP-1c protein expression. The level of SREBP-1c was positively correlated with serum triglyceride in the cells expressing the PNPLA3 I148M variant (r=0.912, P<0.01).

CONCLUSIONThe risk of liver disease associated with the PNPLA3 I148M variant, which increases lipogenesis, may involve SREBP-1c and a pathway that increases triglycerides.

Cell Line, Tumor ; Humans ; Lipase ; Liver Diseases ; Membrane Proteins ; Risk Factors ; Sterol Regulatory Element Binding Protein 1 ; Triglycerides

OBJECTIVETo investigate the cell cycle of Huh-7 cells affected by I148M polymorphism of PNPLA3 gene and the possible mechanisms.

METHODSHuh-7 cells which could respectively overexpress PNPLA3 wild type and I148M variant were cultured and Huh-7 cells with zero load plasmids were used as matched control, Flow cytometry was conducted to detect the cell cycles of these 3 type of Huh-7 cells and western blot and realtime fluorescence quantitative PCR were applied to investigate the expression of regulatory factors (Cyclin D1 and p53) of cell cycle. t-test was used in statistical analysis.

RESULTSCell cycle phase distribution was presented by the proportion of cells in each phases (%), compared with the control group, the cell cycle phase distribution (G1 phase 59.27 ± 0.15, G2/M phase 24.23 ± 0.31, S phases 16.50 ± 0.26) had no differences in wild type group (G1 phase 58.53 ± 0.35, G2/M phase 24.87 ± 0.60, S phases 16.60 ± 0.26; Probability value less than 0.05). While between variant type group and wild type group, G1 phase was significantly decreased (variant type group G phase 38.37 ± 0.21, Probability value less than 0.05), S phase and G2/M phase were increased (variant type group S phase 27.47 ± 0.35, P less than 0.05; G2/M phase 34.17 ± 0.15, P less than 0.05), respectively. compared with control group, the relative expression of P53 mRNA in variant type group was significantly upregulated (control group 1.06 ± 0.41, variant type group 6.54 ± 0.34; Probability value less than 0.05) and there was no statistical significance in wild type group (1.66 ± 0.30, P more than 0.05); Cyclin D1 expression showed no statistical significance in any of these three groups, control group 1.00 ± 0.10, wild type group 1.06 ± 0.03, variant type group, 1.11 ± 0.04; P > 0.05).

CONCLUSIONI148M polymorphism of PNPLA3 gene affects cell cycles of Huh-7 cells via up-regulatating P53.

Carcinoma, Hepatocellular ; Cell Cycle ; Cell Line, Tumor ; Cyclin D1 ; Flow Cytometry ; Humans ; Lipase ; Liver Neoplasms ; Membrane Proteins ; Polymorphism, Genetic

OBJECTIVETo investigate the association between two polymorphisms of the APOC3 gene (T-455C and C-482T) and hereditary risk of non-alcoholic fatty liver disease (NAFLD).

METHODSA total of 287 patients with NAFLD and 310 control subjects were genotyped by PCR and direct sequencing. Serum lipid profiles were also detected by standard biochemical

METHODSOne-hundred-and-eighty of the study participants were used to measure the APOC3 content by enzyme-linked immunosorbent assay. Inter-group differences and associations were assessed statistically using Chi square and t tests and logistic and linear regression analyses.

RESULTSThe frequencies of neither the genotypes or alleles were significantly different between the NAFLD cases and the controls. Compared with the most common genotypes-455TT or-482CC, none of the variants showed a significant increase in risk of NAFLD or for the clinical and biochemical parameters. The adjusted odds ratios (with 95% confidence intervals) of NAFLD were 1.25 (0.79-1.96) and 1.20 (0.76-1.89) for carriers of the APOC3-455C and-482 T variants respectively (P more than 0.05).

CONCLUSIONThe T-455C and C-482T polymorphisms of the APOC3 gene are not associated with risk of NAFLD, pathogenic changes in lipid profiles, or insulin resistance in Han Chinese.

Adult ; Aged ; Alleles ; Apolipoprotein C-III ; genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Insulin Resistance ; Lipids ; blood ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; genetics ; metabolism ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Young Adult

OBJECTIVETo investigate the association between the PNPLA3 rs738409 polymorphism and chronic hepatitis B (CH[B) in a Han Chinese population residing in Qingdao.

METHODSPeripheral blood samples were collected from 185 CHB patients and 164 healthy controls and subjected to polymerase chain reaction (PCR) and DNA sequencing to determine the PNPLA3 genotypes. The relative risk of the rs738409 polymorphism for CHB was estimated by calculating the odds ratio (OR) and 95% confidence interval.

RESULTSThe rs738409 G allele frequency was significantly different between the CHB and control groups (31.9% vs.21.9% respectively, P less than 0.05). Compared to he rs738409 C allele, the G allele was associated with an increased risk of developing CHB (OR =1.67, 95% CI:1.18-2.34, P =0.003). Logistic regression model analysis, with adjustment for confounding factors, indicated that carriers of the PNPLA3 rs738409 GG + GC genotype had increased risk of CHB than carriers of the CC genotype (OR =1.76 ,95% CI:1.14-2.71, P =0.011).

CONCLUSIONQingdao Han Chinese who are carriers of the rs738409 G allele are at increased risk of CHB.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; epidemiology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Hepatitis B, Chronic ; epidemiology ; genetics ; Humans ; Lipase ; genetics ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors ; Young Adult