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

脂肪酸去饱和酶 (FADS) 多态性在测定中的作用/Floyd H.Chilton

• 批准号: 8007049
• 负责人: FLOYD H CHILTON
• 金额: $ 39.53万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8007049
• 关键词: 11q12; 11q12-q13; 13q; Affect; African; African American; Alleles; American; Anabolism; Arachidonic Acids; Asthma; Basophils; Borago; Botanicals; Caucasians; Caucasoid Race; Cells; Chromosomes; Data; Databases; Diabetes Mellitus; Disease; Echium; Effectiveness; Eicosanoid Production; Eicosanoids; Event; Family; Fasting; Fatty Acid Desaturases; Fatty Acids; Flax; Food Interactions; Frequencies; Gene Cluster; Gene Expression; Gene Family; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Grant; Health; Human; Hypertension; Immune; Immunity; Individual; Inflammation; Inflammatory; Influentials; Ingestion; Insulin Resistance; International; Investigation; Island; Laboratories; Lead; Leukocytes; Leukotrienes; Link; Linoleic Acids; Linolenic Acids; Linseed Oil; Lipids; Measures; Messenger RNA; Metabolic; Metabolic syndrome; Metabolism; Minor; Mononuclear; Nutrient; Obesity; Oils; Oleic Acids; Olive oil preparation; Pathway interactions; Patients; Placebos; Plant Oils; Play; Polyunsaturated Fatty Acids; Population; Prevalence; Prevention; Prostaglandins; Proteins; Race; Research; Role; Seeds; Serum; Severities; Signal Transduction; Single Nucleotide Polymorphism; Supplementation; Syndrome; Testing; Thromboxanes; Transcript; Variant; Whole Blood; Work; atopy; base; cohort; desaturase; diabetic; dietary supplements; ethnic difference; fatty acid metabolism; genetic variant; high risk; immune function; indexing; lipid mediator; member; neutrophil; prevent; response; stearidonic acid

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.

目前，有 50-7500 万美国人患有代谢或胰岛素抵抗综合症。一个令人信服的 大量科学证据表明，摄入 w6 和 w3 PUFA 在 预防或诱导多种炎症性疾病，包括代谢综合征/糖尿病。我们的 初步数据表明，多不饱和脂肪酸 (PUFA) 代谢存在重大遗传差异 不同的个人和种族群体。此外，我们的初步数据和其他人的工作表明 染色体 11q12-q13 上脂肪酸去饱和酶 (FADS) 基因簇中的某些等位基因相关 具有较高水平的 PUFA 代谢，可能使某些个人或种族群体面临更高的风险 某些炎症性疾病。我们假设该区域存在单核苷酸多态性（SNP） 也与基于 MC-PUFA 的植物补充剂影响炎症的能力有关 疾病。以此为背景，本提案的总体目标是让人们更好地理解 关于 PUFA 代谢的基因-营养相互作用及其在有效性中的作用 基于植物多不饱和脂肪酸的膳食补充剂。目标 1 研究 FADS 中 SNP 与 非裔美国人和白种人中的中链和长链 w3 和 w6 PUFA 水平和比例 无代谢综合征/糖尿病。 Subaims 将确定跟踪的基因座中的不同基因型如何 与 FADS1 活性密切相关，影响白细胞中基因 mRNA 转录本的表达和蛋白水平 以及免疫细胞功能反应（嗜碱性粒细胞、中性粒细胞和整个细胞产生类二十烷酸） 血;循环单核细胞中炎症基因的表达）。在目标 2 中，我们将研究如何 该 SNP 中的基因型会影响植物补充剂中 PUFA 的代谢，并影响 植物补充剂降低代谢综合征/糖尿病受试者炎症指数的能力。 这项研究的长期目标是获得理解以优化个人的反应 以及使用基于合理营养基因策略的基于 PUFA 的植物补充剂的分组。这可以 最终产生可专门优化个人健康的 MC-PUFA 植物补充剂。