Role of Fatty Acid Desaturase (FADS) Polymorphisms in Determining/Floyd H.Chilton

目前，5000万至7500万美国人患有代谢或胰岛素抵抗综合征。一个令人信服 大量科学证据表明，摄入w 6和w3 PUFA在 预防或诱导多种炎性疾病，包括代谢综合征/糖尿病。我们 初步数据表明，在多不饱和脂肪酸（PUFA）代谢方面， 不同的个体和种族群体。此外，我们的初步数据和其他人的工作表明， 染色体11 q12-q13上脂肪酸去饱和酶（FADS）基因簇中的某些等位基因与 PUFA代谢水平较高，可能使某些个体或种族群体面临更高的风险， 某些炎症性疾病。我们假设该区域的单核苷酸多态性（SNPs） 也将与基于MC-PUFA的植物补充剂影响炎症的能力有关。 疾病在此背景下，本提案的总体目标是更好地了解 基因-营养素相互作用与PUFA代谢及其在有效性中的作用 植物性PUFA膳食补充剂。目的1研究FADS中SNPs与 非裔美国人和高加索人中的中链和长链w3和w 6 PUFA水平和比率， 没有代谢综合征/糖尿病。Subaims将确定一个基因座中的不同基因型如何跟踪 与FADS 1活性密切相关的是影响白细胞中基因mRNA转录本和蛋白水平的表达 以及免疫细胞功能性应答（嗜碱性粒细胞、嗜中性粒细胞和整体细胞产生类花生酸 血液;循环单核细胞中的炎性基因表达）。在目标2中，我们将研究如何 同一SNP中的基因型影响植物补充剂中PUFA的代谢， 植物补充剂降低代谢综合征/糖尿病患者炎症指数的能力。 这项研究的长期目标是获得理解，以优化个人的反应 和组的PUFA为基础的植物补充剂使用合理的营养基因为基础的战略。这可能 最终导致MC-PUFA植物营养素，将专门优化个人的健康。

Currently between 50-75 million Americans have metabolic or insulin resistance syndrome. A convincing body of scientific evidence indicates that the ingestion of w6 and w3 PUFAs plays an important role in the prevention or induction of numerous inflammatory disorders including metabolic syndrome/diabetes. Our preliminary data suggests that there are major genetic differences in poly-unsaturated (PUFA) metabolism in different individuals and racial groups. Furthermore, our preliminary data and the work of others show that certain alleles in the fatty acid desaturase (FADS) gene cluster on chromosome 11q12-q13 are associated with higher levels of PUFA metabolism and may place certain individuals or racial groups at higher risk of certain inflammatory diseases. We hypothesize that single nucleotide polymorphisms (SNPs) in this region will also be associated with the capacity of MC-PUFA-based botanical supplements to impact inflammatory disease. With this as a background, the overall goal of this proposal is to provide a better understanding of gene-nutrient interactions with regard to PUFA metabolism and and their role in the effectiveness of botanical PUFA-based dietary supplements. Aim 1 investigates the association of SNPs in FADS with medium and long chain w3 and w6 PUFA levels and ratios in African Americans and Caucasians with and without metabolic syndrome/diabetes. Subaims will determine how different genotypes in a locus that tracks closely with FADS1 activity affects the expression of gene mRNA transcripts and protein levels in leukocytes as well as immune cell functional responses(eicosanoid generation by basophils, neutrophils and whole blood; inflammatory gene expression in circulating mononuclear cells). In Aim 2, we will investigate how genotypes in this same SNP affects the metabolism of PUFAs in botanical supplements and impacts the capacity of botanical supplements to reduce indices of inflammation in metabolic syndrome/diabetic subjects. The long term-objective of this research is to gain the understanding to optimize the response of individuals and groups to PUFA-based botanical supplements using a rational nutrient-gene based strategy. This could ultimately lead to MC-PUFA botanical supplemnts that would specifically optimize the health of individuals.