McDermott Center for Human Growth and Development, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8591, USA.
Hepatology. 2011 Feb;53(2):467-74. doi: 10.1002/hep.24072. Epub 2010 Dec 10.
Nonalcoholic fatty liver disease (NAFLD) is an escalating health problem that is frequently associated with obesity and insulin resistance. The mechanistic relationship between NAFLD, obesity, and insulin resistance is not well understood. A nonsynonymous variant in patatin-like phospholipase domain containing 3 (rs738409, I148M) has been reproducibly associated with increased hepatic triglyceride content (HTGC) but has not been associated with either the body mass index (BMI) or indices of insulin resistance. Conversely, two sequence variants in apolipoprotein C3 (APOC3) that have been linked to hypertriglyceridemia (rs2854117 C > T and rs2854116 T > C) have recently been reported to be associated with both hepatic fat content and insulin resistance. Here we genotyped two APOC3 variants in 1228 African Americans, 843 European Americans and 426 Hispanics from a multiethnic population based study, the Dallas Heart Study and test for association with HTGC and homeostatic model of insulin resistance (HOMA-IR). We also examined the relationship between these two variants and HOMA-IR in the Atherosclerosis Risk in Communities (ARIC) study. No significant difference in hepatic fat content was found between carriers and noncarriers in the Dallas Heart Study. Neither APOC3 variant was associated with HOMA-IR in the Dallas Heart Study; this lack of association was confirmed in the ARIC study, even after the analysis was restricted to lean (BMI < 25 kg/m(2) ) individuals (n = 4399).
Our data do not support a causal relationship between these two variants in APOC3 and either HTGC or insulin resistance in middle-aged men and women.
非酒精性脂肪性肝病（NAFLD）是一种日益严重的健康问题，常与肥胖和胰岛素抵抗有关。NAFLD、肥胖和胰岛素抵抗之间的机制关系尚不清楚。载脂蛋白 C3（APOC3）中的一个非同义变异（rs738409，I148M）已被反复证明与肝甘油三酯含量（HTGC）增加有关，但与体重指数（BMI）或胰岛素抵抗指数无关。相反，与高甘油三酯血症相关的 APOC3 中的两个序列变异（rs2854117 C > T 和 rs2854116 T > C）最近被报道与肝脂肪含量和胰岛素抵抗均有关。在这里，我们在一个多民族人群的基础研究——达拉斯心脏研究中对 1228 名非裔美国人、843 名欧洲裔美国人和 426 名西班牙裔个体的两个 APOC3 变异进行了基因分型，并检测了它们与 HTGC 和胰岛素抵抗的稳态模型（HOMA-IR）的相关性。我们还在动脉粥样硬化风险社区研究（ARIC）中研究了这两个变异与 HOMA-IR 的关系。在达拉斯心脏研究中，携带者和非携带者之间的肝脂肪含量没有显著差异。这两个 APOC3 变异均与达拉斯心脏研究中的 HOMA-IR 无关；这一缺乏相关性在 ARIC 研究中得到了证实，即使在分析仅限于瘦个体（BMI < 25 kg/m2）时（n = 4399）也是如此。
我们的数据不支持这两个 APOC3 变异与中年男女的 HTGC 或胰岛素抵抗之间存在因果关系。
