Department of Internal Medicine, Università degli Studi Milano, UO Medicina Interna 1B, Ospedale Maggiore Ca' Granda Fondazione Policlinico IRCCS, Milan, Italy.
J Hepatol. 2011 Dec;55(6):1409-14. doi: 10.1016/j.jhep.2011.03.035. Epub 2011 Jul 21.
BACKGROUND & AIMS: The T-455C and C-482T APOC3 promoter region polymorphisms (SNPs) have recently been reported to predispose to dyslipidemia, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) in Indian subjects, but the association with liver damage has not been evaluated so far. The aim was to assess the association between APOC3 SNPs and liver damage in Caucasian patients.
We considered 437 Italian patients with histological diagnosis of NAFLD (including 137 children, 120 morbid obese) and 316 healthy controls, 71 Italian family trios, and 321 patients from the UK. APOC3 SNPs were determined by sequencing, allele-specific oligonucleotide probes and PCR-restriction fragment length polymorphism analysis, hepatic APOC3 mRNA levels by real-time PCR.
APOC3 SNPs were not associated with NAFLD in Italian subjects, although a borderline significance for the transmission of the -455T allele was observed in the family study. Homozygosity for the APOC3 wild-type genotype (APOC3 WT) was associated with a more favorable lipid profile in control subjects, and consistently with lower hepatic APOC3 mRNA levels in obese patients without diabetes. However, APOC3 SNPs, alone or in combination, were not associated with insulin resistance, altered lipid levels, liver enzymes, and with liver damage (severity of steatosis, nonalcoholic steatohepatitis, and moderate/severe fibrosis) in Italian as well as in UK patients, and in the whole cohort. Stratification for the I148M PNPLA3 mutation, associated with the susceptibility to NASH, did not alter the results.
APOC3 genotype is not associated with progressive liver damage in Caucasian patients with NAFLD.
APOC3 启动子区域 T-455C 和 C-482T 多态性（SNP）最近被报道易导致印度人群的血脂异常、胰岛素抵抗和非酒精性脂肪性肝病（NAFLD），但尚未评估其与肝损伤的相关性。本研究旨在评估 APOC3 SNP 与白人患者肝损伤之间的相关性。
我们纳入了 437 例经组织学诊断为 NAFLD 的意大利患者（包括 137 例儿童，120 例病态肥胖患者）和 316 例健康对照者，71 例意大利家系和 321 例来自英国的患者。通过测序、等位基因特异性寡核苷酸探针和 PCR 限制性片段长度多态性分析确定 APOC3 SNP，实时 PCR 检测肝 APOC3 mRNA 水平。
APOC3 SNP 与意大利人群的 NAFLD 无关，尽管在家系研究中观察到-455T 等位基因的传递具有边缘显著性。在对照组中，APOC3 野生型纯合子（APOC3 WT）与更有利的脂质谱相关，且在无糖尿病的肥胖患者中与较低的肝 APOC3 mRNA 水平一致。然而，APOC3 SNP 无论是单独存在还是联合存在，均与意大利和英国患者以及整个队列的胰岛素抵抗、血脂水平改变、肝酶以及肝损伤（脂肪变性严重程度、非酒精性脂肪性肝炎和中度/重度纤维化）无关，且与 PNPLA3 突变（I148M）的分层无关，该突变与 NASH 的易感性相关。
在白人 NAFLD 患者中，APOC3 基因型与进行性肝损伤无关。
