Mirandola Silvia, Osterreicher Christoph H, Marcolongo Moira, Datz Christian, Aigner Elmar, Schlabrakowski Anne, Realdon Stefano, Gerotto Martina, Alberti Alfredo, Stickel Felix
Venetian Institute of Molecular Medicine, Padova, Italy.
Liver Int. 2009 Apr;29(4):557-65. doi: 10.1111/j.1478-3231.2008.01892.x. Epub 2008 Oct 10.
Hepatic steatosis may promote progression of chronic hepatitis C (CHC). Microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of ApoB lipoprotein and is implicated in hepatitis C virus (HCV)-related steatosis. The MTP -493G/T polymorphism may promote liver fat accumulation, but its role in HCV-related steatosis is still unclear.
Two hundred ninety-eight CHC patients were studied and genotyped for MTP -493G/T variants. Hepatic MTP mRNA expression and activity were determined in a subgroup.
Patients with grades 2/3 steatosis were older, had a higher body mass index (BMI), more advanced fibrosis and lower MTP mRNA expression and carried more often HCV genotype 3 and the MTP T allele. Age, BMI, HCV-3 and MTP T allele [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.2-3.53; P=0.009] were independent risk factors for steatosis grades 2/3, and in HCV genotype non-3 patients, the MTP T allele was the strongest predictor for steatosis grade 2/3 (OR 2.17; 95% CI 1.22-3.86; P=0.008). Moreover, TT carriers had higher high-density lipoprotein (65.6+/-14.6 vs 56.1+/-16.2 mg/dl; P=0.003) and apolipoprotein AI (1.80+/-0.3 vs 1.60+/-0.3 g/L; P=0.005) levels than G allele carriers.
Chronic hepatitis C patients with the MTP -493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non-3 patients.
肝脂肪变性可能促进慢性丙型肝炎（CHC）的进展。微粒体甘油三酯转移蛋白（MTP）是载脂蛋白B组装和分泌所必需的，并且与丙型肝炎病毒（HCV）相关的脂肪变性有关。MTP -493G/T多态性可能促进肝脏脂肪堆积，但其在HCV相关脂肪变性中的作用仍不清楚。
对298例CHC患者进行研究，并对MTP -493G/T变异进行基因分型。在一个亚组中测定肝脏MTP mRNA表达和活性。
2/3级脂肪变性患者年龄较大，体重指数（BMI）较高，纤维化更严重，MTP mRNA表达较低，更常携带HCV基因3型和MTP T等位基因。年龄、BMI、HCV-3和MTP T等位基因[比值比（OR）2.05；95%置信区间（CI）1.2-3.53；P=0.009]是2/3级脂肪变性的独立危险因素，在非3型HCV基因患者中，MTP T等位基因是2/3级脂肪变性的最强预测因子（OR 2.17；95%CI 1.22-3.86；P=0.008）。此外，TT携带者的高密度脂蛋白水平（65.6±14.6对56.1±16.2mg/dl；P=0.003）和载脂蛋白AI水平（1.80±0.3对1.60±0.3g/L；P=0.005）高于G等位基因携带者。
携带MTP -493T等位基因的慢性丙型肝炎患者脂肪变性程度更高，表明其对肝脏脂肪堆积有重要影响，尤其是在非3型HCV患者中。
