Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Am J Clin Nutr. 2010 Dec;92(6):1522-7. doi: 10.3945/ajcn.2010.30185. Epub 2010 Oct 20.
Recently, a genetic variant (rs738409; C→G) of the PNPLA3 gene was identified to be associated with increased hepatic fat deposition, and the effect was more pronounced in Hispanics. Animal models have also shown that PNPLA3 expression can be regulated by dietary carbohydrate.
The aim of this study was to examine whether the influence of PNPLA3 genotype on hepatic fat is modulated by dietary factors in Hispanic children.
PNPLA3 was genotyped in 153 Hispanic children (75% female, ages 8-18 y) by using the TaqMan method. Dietary intake was assessed by using three 24-h dietary recalls or diet records. Visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and hepatic fat fraction (HFF) were assessed in multiple abdominal slices by magnetic resonance imaging. Analysis of covariance was used to assess the diet × genotype interaction in liver fat, with the following a priori covariates: sex, age, energy, VAT, and SAAT.
HFF was influenced by a significant interaction between genotype and diet (genotype × carbohydrate, P = 0.04; genotype × total sugar, P = 0.01). HFF was positively related to carbohydrate (r = 0.31, P = 0.04) and total sugar (r = 0.34, P = 0.02) intakes but only in the GG group, independent of covariates. Dietary variables were not related to HFF in the CC or CG group or to other fat depots in all genotype groups.
These findings suggest that Hispanic children carrying the GG genotype are susceptible to increased hepatic fat when dietary carbohydrate intake, specifically sugar, is high. Specific dietary interventions based on genetic predisposition in this population may lead to more effective therapeutic outcomes for fatty liver. This trial was registered at clinicaltrials.gov as NCT00697580, 195-1642394A1, and NCT00693511.
最近，研究人员发现 PNPLA3 基因的一个遗传变异（rs738409；C→G）与肝内脂肪沉积增加有关，而且这种影响在西班牙裔人群中更为明显。动物模型也表明，PNPLA3 的表达可以受到饮食中碳水化合物的调节。
本研究旨在探讨在西班牙裔儿童中，PNPLA3 基因型对肝内脂肪的影响是否受饮食因素的调节。
采用 TaqMan 法对 153 名西班牙裔儿童（75%为女性，年龄 8-18 岁）进行 PNPLA3 基因分型。通过 3 次 24 小时膳食回顾或饮食记录评估饮食摄入。采用磁共振成像对多个腹部切片进行内脏脂肪组织（VAT）、腹部皮下脂肪组织（SAAT）和肝脂肪分数（HFF）的评估。采用协方差分析评估肝脂肪的饮食-基因型相互作用，预先设定的协变量包括性别、年龄、能量、VAT 和 SAAT。
HFF 受到基因型与饮食之间显著的相互作用影响（基因型×碳水化合物，P = 0.04；基因型×总糖，P = 0.01）。HFF 与碳水化合物（r = 0.31，P = 0.04）和总糖（r = 0.34，P = 0.02）的摄入量呈正相关，但仅在 GG 组中存在这种相关性，且不受其他因素的影响。在 CC 或 CG 组中，饮食变量与 HFF 或所有基因型组的其他脂肪沉积均无相关性。
这些发现表明，携带 GG 基因型的西班牙裔儿童在摄入高碳水化合物（尤其是糖）时，肝内脂肪更容易增加。基于该人群的遗传易感性进行特定的饮食干预可能会为治疗脂肪肝带来更有效的治疗效果。本试验在 clinicaltrials.gov 注册，编号为 NCT00697580、195-1642394A1 和 NCT00693511。
