Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
PLoS One. 2012;7(5):e37827. doi: 10.1371/journal.pone.0037827. Epub 2012 May 21.
A single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake.
We studied 127 children and adolescents (56 boys, 71 girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7±3.3; mean BMI 30.7±7.2). The dietary composition was assessed by the Nutrition Data System for Research (NDS-R version 2011). The patients underwent a MRI study to assess the liver fat content (HFF%), ALT measurement and the genotyping of the rs738409 SNP by automatic sequencing.
As previously observed, HFF% and ALT levels varied according to the genotype in each ethnicity. ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects homozygote for the G allele of the rs738409 (r2 = 0.45, p = 0.001 and r2 = 0.40, p = 0.006, respectively).
These findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype.
最近的研究表明，载脂蛋白样磷脂酶 3 基因（PNPLA3）中的单核苷酸多态性（SNP）rs738409 与成年人和儿童的肝脂肪变性和 ALT 水平升高有关。鉴于 PNPLA3 在脂肪肝发展中的潜在作用，我们旨在探讨 PNPLA3 基因型对肥胖青少年肝脏脂肪的影响是否可能受到饮食因素的调节，如必需的欧米伽多不饱和脂肪酸（PUFA）的摄入。
我们研究了 127 名儿童和青少年（56 名男孩，71 名女孩；58 名白种人；30 名非裔美国人，39 名西班牙裔；平均年龄 14.7±3.3；平均 BMI 30.7±7.2）。饮食组成通过营养数据系统进行评估（NDS-R 版本 2011）。对患者进行 MRI 研究以评估肝脂肪含量（HFF%）、ALT 测量和 rs738409 SNP 的自动测序。
正如之前观察到的，HFF%和 ALT 水平根据每种族的基因型而变化。ALT 水平和 HFF%受到基因型与 ω-6/ω-3 PUFA 比值（n-6/n-3）之间相互作用的显著影响，p=0.003 和 p=0.002。事实上，只有在 rs738409 的 G 等位基因纯合子的受试者中，HFF%和 ALT 水平才与 n-6/n-3 的消耗有关（r2=0.45，p=0.001 和 r2=0.40，p=0.006）。
这些发现表明，富含 n-6/n-3 PUFA 的饮食与肥胖青少年的脂肪肝和肝损伤之间的关联可能是由易感基因型驱动的。
