Departamento de Gastroenterologia, Universidade de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2012 Jan;45(1):72-7. doi: 10.1590/s0100-879x2011007500160. Epub 2011 Dec 9.
The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.
肝微粒体转移蛋白 (MTP) 活性降低可导致脂肪肝,从而加重慢性丙型肝炎 (CHC) 患者的肝脂肪变性和纤维化。MTP 基因启动子-493G/T 的 G 等位基因与 T 等位基因相比,转录活性较低。我们研究了这种关联与 CHC 患者的代谢和组织学变量之间的关系。采用聚合酶链反应直接测序法对 174 例未经治疗的 CHC 患者进行 MTP-493G/T 基因分型。所有患者均为威尔逊病、血色病和自身免疫性疾病标志物阴性,且目前和过去的每日酒精摄入量低于 100g/周。样本分布符合 Hardy-Weinberg 平衡。在基因型 1 的受试者中,纤维化程度为 3+4 的患者中有 56.8%至少携带一个 G 等位基因,而纤维化程度为 1+2 的患者中有 34.3%(OR=1.8;95%CI=1.3-2.3)。以脂肪变性为因变量的逻辑回归分析确定 GG+GT 基因型是脂肪变性的独立保护因素(OR=0.4,95%CI=0.2-0.8;P=0.01)。结果表明,MTP-493G/T 中 G 等位基因的存在与较低的肝 MTP 表达相关,可保护我们的 CHC 患者免受脂肪变性的影响。