Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain.
Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
Nutrition. 2018 Mar;47:83-89. doi: 10.1016/j.nut.2017.10.008. Epub 2018 Jan 4.
The aim of this study was to investigate the influence of two PPARGC1A gene polymorphisms on metabolic outcomes in response to two energy-restricted diets.
A 4-mo nutritional intervention was conducted that involved two different hypo-energetic diets based on low-fat (LF) and moderately high-protein (MHP) dietary patterns. Unrelated subjects with excessive weight were genotyped for two PPARGC1A polymorphisms: Rs8192678 (Gly482Ser) and rs3755863 (G > A). Genotyping was performed by next-generation sequencing and haplotypes were screened. Anthropometric measurements and biochemical tests were assessed with standardized methods.
Different cholesterol outcomes were observed by diet and Gly482Ser genotype. The Gly482 Gly homozygotes after an LF diet had lower reductions in total cholesterol (-9 mg/dL vs. -27 mg/dL; P = 0.017) and low-density lipoprotein cholesterol levels (-5 mg/dL vs. -18 mg/dL; P = 0.016) than the subjects who were carriers of 482 Ser allele. However, this finding was not recorded in the MHP group where Gly482 Gly homozygotes underwent similar cholesterol decreases as the 482 Ser allele carriers. Likewise, all genotype carriers had significant reductions in the frequencies of hypercholesterolemia (total cholesterol ≥200 mg/dL) except for Gly482 Gly homozygotes in the LF group. Meanwhile, the rs3755863 polymorphism and PPARGC1A haplotypes showed borderline effects with regard to cholesterol decreases.
An energy-restricted MHP diet might be more beneficial than an LF diet to reduce serum cholesterol among subjects who are carriers of the PPARGC1A Gly482Gly genotype. The analysis of this genetic variant might be the basis for a precise, nutrigenetic management of hypercholesterolemia based on genetic makeup.
本研究旨在探讨两种过氧化物酶体增殖物激活受体 γ 共激活因子 1A（PPARGC1A）基因多态性对两种能量限制饮食的代谢结果的影响。
进行了为期 4 个月的营养干预，包括两种基于低脂肪（LF）和中高蛋白（MHP）饮食模式的低能量饮食。对超重的非相关个体进行了两种 PPARGC1A 多态性的基因分型：rs8192678（Gly482Ser）和 rs3755863（G > A）。基因分型通过下一代测序进行，筛选单倍型。采用标准化方法评估体重指数和生化指标。
不同的胆固醇结果与饮食和 Gly482Ser 基因型有关。LF 饮食后，Gly482 Gly 纯合子的总胆固醇（-9mg/dL 与-27mg/dL；P=0.017）和低密度脂蛋白胆固醇水平（-5mg/dL 与-18mg/dL；P=0.016）降低幅度低于携带 482 Ser 等位基因的个体。然而，在 MHP 组中并未记录到这种现象，Gly482 Gly 纯合子与携带 482 Ser 等位基因的个体发生了类似的胆固醇降低。同样，除了 LF 组的 Gly482 Gly 纯合子外，所有基因型携带者的高胆固醇血症（总胆固醇≥200mg/dL）的频率均显著降低。与此同时，rs3755863 多态性和 PPARGC1A 单倍型对胆固醇降低具有边缘效应。
对于携带 PPARGC1A Gly482Gly 基因型的个体，限制能量的 MHP 饮食可能比 LF 饮食更有利于降低血清胆固醇。对这种遗传变异的分析可能是基于遗传构成的精确营养遗传学管理高胆固醇血症的基础。
