Nutrigenomics Research Group, School of Public Health and Population Science, University College Dublin Conway Institute, University College, Dublin 4, Ireland.
J Nutr. 2010 Feb;140(2):238-44. doi: 10.3945/jn.109.115329. Epub 2009 Dec 23.
The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPR polymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). LEPR rs3790433 GG homozygotes had increased MetS risk compared with the minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05-2.57; P = 0.028], which may be accounted for by their increased risk of elevated insulin concentrations (OR 2.40; 95% CI: 1.28-4.50; P = 0.006) and insulin resistance (OR = 2.15; 95% CI: 1.18-3.90; P = 0.012). Low (less than median) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92-2.94) and insulin resistance (OR 3.40-3.47). Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for the LEPR rs3790433 G allele was associated with insulin resistance, which may predispose to increased MetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA.
瘦素受体（LEPR）与胰岛素抵抗有关，而胰岛素抵抗是代谢综合征（MetS）的一个关键特征。基因-脂肪酸的相互作用可能会影响 MetS 的发病风险。本研究旨在调查 LEPR 多态性、胰岛素抵抗与 MetS 风险之间的关系，以及血浆脂肪酸（膳食脂肪酸的生物标志物）是否可以调节这种关系。在 MetS 病例和匹配对照（n=1754）的 LIPGENE-SU.VI.MAX 研究中，测定了 LEPR 多态性（rs10493380、rs1137100、rs1137101、rs12067936、rs1805096、rs2025805、rs3790419、rs3790433、rs6673324 和 rs8179183）、生化测量和血浆脂肪酸谱。与携带次要 A 等位基因的个体相比，LEPR rs3790433 GG 纯合子的 MetS 发病风险更高[比值比（OR）=1.65；95%置信区间（CI）：1.05-2.57；P=0.028]，这可能是由于其升高的胰岛素浓度（OR 2.40；95%CI：1.28-4.50；P=0.006）和胰岛素抵抗（OR=2.15；95%CI：1.18-3.90；P=0.012）风险所致。低（低于中位数）血浆（n-3）和高（n-6）多不饱和脂肪酸（PUFA）状态加剧了 GG 纯合子对高胰岛素血症（OR 2.92-2.94）和胰岛素抵抗（OR 3.40-3.47）的遗传风险。有趣的是，在高（n-3）或低（n-6）PUFA 背景下，这些关联被消除了。重要的是，我们在一个独立的队列中复制了其中的一些发现。LEPR rs3790433 的 GG 纯合子与胰岛素抵抗有关，这可能使 MetS 的发病风险增加。LEPR rs3790433 与多不饱和脂肪酸之间的新基因-营养相互作用表明，在血浆（n-3）或（n-6）多不饱和脂肪酸水平较低或较高的个体中，这些遗传影响更为明显。
