ABSTRACT
Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.
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OBJECTIVE: To review the pharmacological actions and related clinical research about the efficacy and safety of lomitapide, which is a new kind of medication for cholesterol disorder-microsomal triglyceride transfer protein inhibitor. METHODS: The domestic and oversea pertinent literatures since 2007 were searched. RESULTS: Lomitapide can performe well in clinic effects and tolerance for homozygous familial hypercholesterolemia. CONCLUSION: Lomitapide can be an effective adjuvant for patients with homozygous familial hypercholesterolemia.
ABSTRACT
Microsomal triglyceride transfer protein (MTP) is a key transfer protein in lipid metabolism and is mainly expressed in the hepatocytes and enterocytes.It plays an important role in transferring triglyceride as well as in assembly and secretion of very low density lipoprotein.Recent studies have shown that MTP is closely related to the onset and development of non-alcoholic fatty liver disease.
ABSTRACT
BACKGROUND/AIMS: A polymorphism in the microsomal triglyceride transfer protein (MTP) is associated with hepatic fibrosis, and carriers showed higher levels of steatosis, higher levels of hepatitis C virus (HCV) RNA and advanced fibrosis. The aim of this study was to study MTP expression pattern in HCV patients and impact of the MTP polymorphism on the response to antiviral therapy. METHODS: One hundred consecutive naive HCV genotype 4 patients were recruited to receive antiviral therapy, and 40 control subjects were also recruited. Demographic, laboratory, and histopathology data were collected. DNA was isolated, and the samples were subjected to polymerase chain reaction analysis and genotyping for MTP by restriction fragment length polymorphism analysis. RESULTS: Patients and controls were age- and sex-matched (male/female, 56/44, age, 39.2+/-7.8 years for patients with HCV; male/female, 18/22, age, 38.1+/-8.1 years for controls). MTP single nucleotide polymorphisms (SNPs) (GG, GT, TT) and alleles (G, T) in the patients versus the controls were 70%, 21%, 9% & 80.5%, 19.5% versus 10%, 87.5%, 2.5% & 53.8%, 46.3%, respectively (p=0.0001). The sustained viral response (SVR) of the patients was 60%. SNPs in MTP genotypes (GG, GT, and TT) and alleles (G and T) in the responders and nonresponders were 71.7%, 25%, 3.3% & 84.2%, 15.8% versus 67.5%, 15%, 17.5% & 75%, 25% (p=0.038 and p=0.109, respectively). A multivariate analysis showed that the GT genotype was an independent predictor of SVR (area under the curve 90% and p=0.0001). CONCLUSIONS: MTP could be a new predictor for SVR to antiviral therapy in patients with HCV genotype 4 infection.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antiviral Agents/therapeutic use , Carrier Proteins/genetics , Case-Control Studies , Egypt , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , RNA, Viral/blood , Treatment Outcome , Viral LoadABSTRACT
Objective To explore the effect of hepatitis B virus(HBV) on the expression of apolipoprotein B(ApoB) and its regulatory mechanism. Methods mRNA and protein expression of ApoB in HepG2 and HepG2.2.15 cells was measured by RT-PCR and Western blot, serum ApoB levels in patients with HBV infection and in healthy individuals were measured by biochemical analyzer Olympus 5400, the expression of ApoB difference among healthy individuals, patients with chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma were analyzed, HBV infectious clone pHBV1.3 was tranfected into HepG2 cells,and expression of ApoB and microsomal triglyceride transfer protein(MTP) was measured by RT-PCR and Western blot. Results Expression of ApoB mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells, serum apoB levels was much lower in patients with chronic hepatitis B and liver cirrhosis as compared to healthy individuals( P ＜0.05 ), HBV could inhibit the expression of ApoB and MTP at mRNA and protein levels. Conclusion HBV may downregulate the synthesis and secretion of ApoB via inhibits the expression of MTP.
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Objective: To investigate how fatty liver was developed in ventromedial hypothalamus(VMH)-lesioned obese rats. Methods: Two groups of rats were prepared: (1)VMH-lesioned obese rats, and (2)sham VMH-lesioned rats. One week after VMH lesions, livers of all rats were isolated for morphological observation and for determination of microsomal triglyceride transfer protein(MTP), phosphatidate phyosphohydrolase (PAP), malic enzyme (ME), and glucose-6-phosphate dehydrogenase(G6PDH). Results: Triglyceride contents in livers of VMH-lesoned obese rats increased significantly, and were about 1.8-fold of control group. Activities of ME, G6PDH and PAP in the livers were also enhanced markedly compared to their controls. Many lipid droplets in cytoplasm of hepatocytes from VMH-lesioned obese rats were observed, while there was no similar finding in hepatocytes of control rats. MTP activity in livers of VMH-lesioned obese rats was higher than that in livers of sham-operated non-obese rats [0.201?0.013 vs. 0.175?0.014 ?g/(mg protein?h),[WTBX]P0.05). Conclusion: Hepatic triglyceride production and activity of MTP were increased in VMH-lesioned obese rats, but magnitude of the latter did not exceed the former. This resulted in hepatic triglyceride accumulation in spite of increase in transport of triglyceride out of liver by MTP. This may contribute to the development of fatty liver in VMH-lesioned obese rats.