Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21225, USA.
Am J Clin Nutr. 2013 Jun;97(6):1395-402. doi: 10.3945/ajcn.112.052183. Epub 2013 May 1.
Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants.
The objective of the study was to identify common genetic variants that are associated with macronutrient intake.
We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 × 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data.
A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (β ± SE: 0.25 ± 0.04%; P = 1.68 × 10(-8)) and lower fat (β ± SE: -0.21 ± 0.04%; P = 1.57 × 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (β ± SE: 0.10 ± 0.02%; P = 9.96 × 10(-10)), independent of BMI (after adjustment for BMI, β ± SE: 0.08 ± 0.02%; P = 3.15 × 10(-7)).
Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).
个体之间的宏量营养素摄入量有很大差异，有证据表明这种差异部分归因于遗传变异。
本研究的目的是确定与宏量营养素摄入相关的常见遗传变异。
我们对欧洲血统人群进行了 2 阶段全基因组关联（GWA）荟萃分析，以评估宏量营养素的摄入量。通过使用食物频率问卷评估宏量营养素，并将其分析为总能量消耗中来自总脂肪、蛋白质和碳水化合物的百分比。从发现 GWA（n = 38360）中，确定了 35 个与宏量营养素摄入相关的独立位点，P < 5 × 10（-6），并在来自 DietGen 联盟的另外 3 个队列（n = 33533）中进行了复制。对于一个位于染色体 19 位的基因（FTO），在包含 Illumina MetaboChip 基因型数据的队列（n = 7724）中提供了额外的复制数据。
位于 19 号染色体的一个变异体（rs838145）与更高的碳水化合物（β ± SE：0.25 ± 0.04%；P = 1.68 × 10（-8））和更低的脂肪（β ± SE：-0.21 ± 0.04%；P = 1.57 × 10（-9））消耗有关。该区域的一个候选基因，成纤维细胞生长因子 21（FGF21），编码一种参与葡萄糖和脂质代谢的成纤维细胞生长因子。该基因座的变异与循环 FGF21 蛋白浓度相关（P < 0.05），但与血液或大脑中的 FGF21 mRNA 浓度无关。FTO 变异（rs1421085）的 BMI 增加等位基因与蛋白质摄入增加相关（β ± SE：0.10 ± 0.02%；P = 9.96 × 10（-10）），与 BMI 无关（调整 BMI 后，β ± SE：0.08 ± 0.02%；P = 3.15 × 10（-7））。
我们的研究结果表明，参与营养代谢和肥胖的基因中的变异与人类的宏量营养素消耗有关。与该研究相关的试验在 clinicaltrials.gov 上注册为 NCT00005131（社区动脉粥样硬化风险研究）、NCT00005133（心血管健康研究）、NCT00005136（家庭心脏研究）、NCT00005121（弗雷明汉心脏研究）、NCT00083369（甘油三酯的遗传和环境决定因素）、NCT01331512（InCHIANTI 研究）和 NCT00005487（多民族动脉粥样硬化研究）。
