Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism,and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. Methods: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. Results: The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%,and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. Conclusions: The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls. (Clin Mol Hepatol 2012;18:295-301)
Abstract
Background/Aims: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism,and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. Methods: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. Results: The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%,and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. Conclusions: The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls. (Clin Mol Hepatol 2012;18:295-301)
참고문헌 (25)
- Kwon SY, "Epidemiology and prevention of hepatitis B virus infection", Korean J Hepatol, 17, pp.87~95 (2011)
- 최혜진, "Clinical features of acute viral hepatitis B in Korea: a multi-center study", Clinical and Molecular Hepatology, 17(4), pp.307~312 (2011), 대한간학회
- Cheong JY, "Genetic polymorphism of interferon-gamma, interferon-gamma receptor, and interferon regulatory factor-1 genes in patients with hepatitis B virus infection", Biochem Genet, 44, pp.246~255 (2006)
- Cheong JY, "Association between chronic hepatitis B virus infection and interleukin- 10, tumor necrosis factor-alpha gene promoter polymorphisms", J Gastroenterol Hepatol, 21, pp.1163~1169 (2006)
- Minihane AM, "ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation", Proc Nutr Soc, 66, pp.183~197 (2007)
- Jofre-Monseny L, "Impact of apoE genotype on oxidative stress, inflammation and disease risk", Mol Nutr Food Res, 52, pp.131~145 (2008)
- Mahley RW, "Apolipoprotein E: far more than a lipid transport protein", Annu Rev Genomics Hum Genet, 1, pp.507~537 (2000)
- Corder EH, "Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families", Science, 261, pp.921~923 (1993)
- Bennet AM, "Association of apolipoprotein E genotypes with lipid levels and coronary risk", JAMA, 298, pp.1300~1311 (2007)
- Wozniak MA, "Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus", Hepatology, 36, pp.456~463 (2002)
- Mueller T, "Apolipoprotein E4 allele is associated with poor treatment response in hepatitis C virus (HCV) genotype 1", Hepatology, 38, pp.1582~1593 (2003)
- Toniutto P, "Genetic polymorphism at the apolipoprotein E locus affects the outcome of chronic hepatitis B", J Med Virol, 82, pp.224~331 (2010)
- Agnello V, "Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor", Proc Natl Acad Sci U S A, 96, pp.12766~12771 (1999)
- Pumeechockchai W, "Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody", J Med Virol, 68, pp.335~342 (2002)
- Mazumdar B, "Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes", Hepatology, 54, pp.1149~1156 (2011)
- Stefas I, "Hepatitis B virus Dane particles bind to human plasma apolipoprotein H", Hepatology, 33, pp.207~217 (2001)
- Mehdi H, "Hepatitis B virus surface antigen binds to apolipoprotein H", J Virol, 68, pp.2415~2424 (1994)
- Rosenthal N, "In search of perverse polymorphisms", N Engl J Med, 338, pp.122~124 (1998)
- Wu AL, "Relative contributions by liver and intestine to individual plasma apolipoproteins in the rat", J Biol Chem, 254, pp.7316~7322 (1979)
- Kelly ME, "Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes: production of interleukin 2 with reduced biological activity", Cell Immunol, 159, pp.124~139 (1994)
- Shiri-Sverdlov R, "Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates", J Hepatol, 44, pp.732~741 (2006)
- Li L, "Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors", J Lipid Res, 49, pp.1782~1793 (2008)
- Bell LN, "Serum proteomic profiling in patients with druginduced liver injury", Aliment Pharmacol Ther, 35, pp.600~612 (2012)
- Blanc JF, "Proteomic analysis of differentially expressed proteins in hepatocellular carcinoma developed in patients with chronic viral hepatitis C", Proteomics, 5, pp.3778~3789 (2005)
- Ritorto MS, "Combined serum and tissue proteomic study applied to a c-Myc transgenic mouse model of hepatocellular carcinoma identified novel disease regulated proteins suitable for diagnosis and therapeutic intervention strategies", J Proteome Res, 10, pp.3012~3030 (2011)