University College Dublin, Dublin, Ireland.
Am J Clin Nutr. 2010 Mar;91(3):794-801. doi: 10.3945/ajcn.2009.28255. Epub 2009 Dec 23.
Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits.
Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics.
Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) case-control study (http://www.ucd.ie/lipgene).
Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls.
A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00429195.
代谢综合征（MetS）的进展由遗传和环境因素决定。基因-环境相互作用可能在调节对 MetS 特征发展的易感性方面起着重要作用。
检查 MetS 受试者中的基因-营养素相互作用，以确定脂联素基因（ADIPOQ）及其受体（ADIPOR1 和 ADIPOR2）中的单核苷酸多态性（SNP）与血浆脂肪酸组成之间的相互作用及其对 MetS 特征的影响。
在参加 LIPGENE（饮食、基因组学和代谢综合征：营养、农业食品、社会和经济综合分析）饮食干预研究的 451 名 MetS 受试者的横断面分析中确定了血浆脂肪酸组成、胰岛素敏感性、血浆脂联素和脂质浓度以及 ADIPOQ、ADIPOR1 和 ADIPOR2 SNP 基因型，并在 LIPGENE-SU.VI.MAX（补充抗氧化维生素和矿物质）病例对照研究（http://www.ucd.ie/lipgene）中的 1754 名受试者中重复检测。
在该队列中检测到单 SNP 效应。在 ADIPOQ 中的 rs266729 和 ADIPOR1 中的 rs10920533 这 2 个 SNP 的基因型之间，三酰甘油、非酯化脂肪酸和腰围存在显著差异。这两个 SNP 的次要等位基因纯合子被确定为具有胰岛素抵抗程度，通过胰岛素抵抗的稳态模型评估来衡量，对血浆饱和脂肪酸（SFAs）的差异高度敏感。ADIPOR1 rs10920533 与胰岛素抵抗之间的 SFA 依赖性关联在来自另一个独立研究的 MetS 病例中得到复制，而在对照中则没有这种关联。
预计降低 MetS 受试者血浆 SFAs 可降低携带 ADIPOQ 中的 rs266729 和 ADIPOR1 中的 rs10920533 次要等位基因的个体的胰岛素抵抗。可以建议向这些个体提供减少 SFA 消耗的个性化饮食建议，作为改善胰岛素敏感性的可能治疗措施。该试验在 clinicaltrials.gov 上注册为 NCT00429195。
