A Polymorphism in the Microsomal Triglyceride Transfer Protein Can Predict the Response to Antiviral Therapy in Egyptian Patients with Chronic Hepatitis C Virus Genotype 4 Infection
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: A polymorphism in the microsomal tri-glyceride transfer protein (MTP) is associated with hepatic fi-brosis, 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 polymor-phism 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 anti-viral therapy in patients with HCV genotype 4 infection.
Abstract
Background/Aims: A polymorphism in the microsomal tri-glyceride transfer protein (MTP) is associated with hepatic fi-brosis, 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 polymor-phism 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 anti-viral therapy in patients with HCV genotype 4 infection.
참고문헌 (23)
- Bressler BL, "High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C", Hepatology, 38, pp.639~644 (2003)
- Szanto P, "Steatosis in hepatitis C virus infection. Response to anti-viral therapy", J Gastrointestin Liver Dis, 15, pp.117~124 (2006)
- Wetterau JR, "Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex", J Biol Chem, 265, pp.9800~9807 (1990)
- Borén J, "Apo B100-containing lipoproteins are secreted by the heart", J Clin Invest, 101, pp.1197~1202 (1998)
- Gordon DA, "Secretion of apolipoprotein B-containing lipoproteins from HeLa cells is dependent on expression of the microsomal triglyceride transfer protein and is regulated by lipid availability", Proc Natl Acad Sci U S A, 91, pp.7628~7632 (1994)
- Leiper JM, "Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells", J Biol Chem, 269, pp.21951~21954 (1994)
- Wetterau JR, "An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits", Science, 282, pp.751~754 (1998)
- Bernard S, "Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes", Diabetologia, 43, pp.995~999 (2000)
- Namikawa C, "Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis", J Hepatol, 40, pp.781~786 (2004)
- Mirandola S, "Hepatic steatosis in hepatitis C is a storage disease due to HCV interaction with microsomal triglyceride transfer protein (MTP)", Nutr Metab (Lond), 7, pp.13~ (2010)
- Richardson MM, "A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C", J Med Genet, 42, pp.e45~ (2005)
- Zampino R, "Microsomal triglyceride transfer protein (MTP) -493G", T gene polymorphism contributes to fat liver accumulation in HCV genotype 3 infected patients, 2008, pp.15, 740~746
- "Hepatitis C in Egypt" (2006)[URL]
- "Annual report 2007" (2007)[URL]
- Houldsworth A, "Polymorphisms in the IL-12B gene and outcome of HCV infection", J Interferon Cytokine Res, 25, pp.271~276 (2005)
- Jun DW, "Polymorphisms of microsomal triglyceride transfer protein gene and phosphatidylethanolamine N-methyltransferase gene in alcoholic and nonalcoholic fatty liver disease in Koreans", Eur J Gastroenterol Hepatol, 21, pp.667~672 (2009)
- Hashemi M, "Association of polymorphisms in glutamate-cysteine ligase catalytic subunit and microsomal triglyceride transfer protein genes with nonalcoholic fatty liver disease", DNA Cell Biol, 30, pp.569~575 (2011)
- Petit JM, "Lack of association between microsomal triglyceride transfer protein gene polymorphism and liver steatosis in HCV-infected patients", Mol Genet Metab, 88, pp.196~198 (2006)
- El-Koofy NM, "Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children", Saudi J Gastroenterol, 17, pp.265~270 (2011)
- Yang ZT, "Polymorphisms of microsomal triglyceride transfer protein in different hepatitis B virusinfected patients", World J Gastroenterol, 14, pp.5454~5460 (2008)
- Karpe F, "A common functional polymorphism in the promoter region of the microsomal triglyceride transfer protein gene influences plasma LDL levels", Arterioscler Thromb Vasc Biol, 18, pp.756~761 (1998)
- García-García AB, "Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia", Pharmacogenet Genomics, 15, pp.211~218 (2005)
- Berg T, "Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy", Hepatology, 37, pp.600~609 (2003)