肝脂肪变性与肝纤维化之间的共同遗传效应：一项前瞻性双生子研究。
Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study.
作者信息
Cui Jeffrey, Chen Chi-Hua, Lo Min-Tzu, Schork Nicholas, Bettencourt Ricki, Gonzalez Monica P, Bhatt Archana, Hooker Jonathan, Shaffer Katherine, Nelson Karen E, Long Michelle T, Brenner David A, Sirlin Claude B, Loomba Rohit
机构信息
NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA.
Department of Radiology, University of California at San Diego, La Jolla, CA.
出版信息
Hepatology. 2016 Nov;64(5):1547-1558. doi: 10.1002/hep.28674. Epub 2016 Jul 25.
UNLABELLED
Nonalcoholic fatty liver disease is associated with metabolic risk factors including hypertension and dyslipidemia and may progress to liver fibrosis. Studies have shown that hepatic steatosis and fibrosis are heritable, but whether they have a significant shared gene effect is unknown. This study examined the shared gene effects between hepatic steatosis and fibrosis and their associations with metabolic risk factors. This was a cross-sectional analysis of a prospective cohort of well-characterized, community-dwelling twins (45 monozygotic, 20 dizygotic twin pairs, 130 total subjects) from southern California. Hepatic steatosis was assessed with magnetic resonance imaging-proton density fat fraction and hepatic fibrosis with magnetic resonance elastography. A standard bivariate twin additive genetics and unique environment effects model was used to estimate the proportion of phenotypic variance between two phenotypes accounted for by additive genetic effects and individual-specific environmental effects. Genetic correlations estimated from this model represent the degree to which the genetic determinants of two phenotypes overlap. Mean (± standard deviation) age and body mass index were 47.1 (±21.9) years and 26.2 (±5.8) kg/m , respectively. Among the cohort, 20% (26/130) had hepatic steatosis (magnetic resonance imaging-proton density fat fraction ≥5%), and 8.2% (10/122) had hepatic fibrosis (magnetic resonance elastography ≥3 kPa). Blood pressure (systolic and diastolic), triglycerides, glucose, homeostatic model assessment of insulin resistance, insulin, hemoglobin A1c, and low high-density lipoprotein had significant shared gene effects with hepatic steatosis. Triglycerides, glucose, homeostatic model assessment of insulin resistance, insulin, hemoglobin A1c, and low high-density lipoprotein had significant shared gene effects with hepatic fibrosis. Hepatic steatosis and fibrosis had a highly significant shared gene effect of 0.756 (95% confidence interval 0.716-1, P < 0.0001).
CONCLUSIONS
Genes involved with steatosis pathogenesis may also be involved with fibrosis pathogenesis. (Hepatology 2016;64:1547-1558).
未标注
非酒精性脂肪性肝病与包括高血压和血脂异常在内的代谢风险因素相关，且可能进展为肝纤维化。研究表明，肝脂肪变性和肝纤维化具有遗传性，但它们是否存在显著的共同基因效应尚不清楚。本研究探讨了肝脂肪变性和肝纤维化之间的共同基因效应及其与代谢风险因素的关联。这是一项对来自南加州的特征明确的社区居住双胞胎前瞻性队列（45对同卵双胞胎，20对异卵双胞胎，共130名受试者）的横断面分析。采用磁共振成像 - 质子密度脂肪分数评估肝脂肪变性，磁共振弹性成像评估肝纤维化。使用标准的双变量双胞胎加性遗传和独特环境效应模型来估计两种表型之间由加性遗传效应和个体特异性环境效应所解释的表型方差比例。从该模型估计的遗传相关性代表两种表型的遗传决定因素重叠的程度。平均（±标准差）年龄和体重指数分别为47.1（±21.9）岁和26.2（±5.8）kg/m²。在该队列中，20%（26/130）有肝脂肪变性（磁共振成像 - 质子密度脂肪分数≥5%），8.2%（10/122）有肝纤维化（磁共振弹性成像≥3 kPa）。血压（收缩压和舒张压）、甘油三酯、葡萄糖、胰岛素抵抗稳态模型评估、胰岛素、糖化血红蛋白A1c以及低高密度脂蛋白与肝脂肪变性有显著的共同基因效应。甘油三酯、葡萄糖、胰岛素抵抗稳态模型评估、胰岛素、糖化血红蛋白A1c以及低高密度脂蛋白与肝纤维化有显著的共同基因效应。肝脂肪变性和肝纤维化有高度显著的共同基因效应，为0.756（95%置信区间0.716 - 1，P < 0.0001）。
结论
参与脂肪变性发病机制的基因可能也参与纤维化发病机制。（《肝脏病学》2016年；64:1547 - 1558）
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