Effect of FADS gene variants on fatty acid synthesis & brain development in India

FADS基因变异对脂肪酸合成的影响

基本信息

批准号：
8211534
负责人：
FLOYD H CHILTON
金额：
$ 12.77万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-06 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8211534
关键词：
Academy Adult Africa African Age Alleles Animals Arachidonic Acids Area Attention Attention deficit hyperactivity disorder Autistic Disorder Behavioral Biochemical Markers Biochemistry Bipolar Disorder Blood Circulation Brain Central America Child Cities Cognitive Collaborations Country DNA Data Dental Developing Countries Development Diet Disease Docosahexaenoic Acids Doctor of Philosophy Embryo Environment European Eye Development Face Fatty Acids Fatty acid glycerol esters Fetus Food Food Analysis Frequencies Future Gene Cluster Gene Frequency Genetic Markers Genetic Variation Genomics Genotype Health Sciences Human Human Development Hyperactive behavior India Infant Institutes Laboratories Malnutrition Medical Medium chain fatty acid Mental disorders Methods Molecular Mothers Mutation Nutritional Nutritional status Oils Pattern Photoreceptors Plant Oils Plants Polyunsaturated Fatty Acids Population Preparation Public Health Religion and Spirituality Research Research Infrastructure Research Personnel Science Scientist South America Southeastern Asia Synapses Techniques Technology Therapeutic Training Training and Infrastructure Universities Visual base blood lipid combat dietary supplements early childhood fatty acid biosynthesis fetal forest medical schools nervous system disorder nutrition pregnant pressure programs sample fixation

项目摘要

DESCRIPTION (provided by applicant): Long-chain polyunsaturated fatty acid (LC-PUFA), such as docosahexaenoic acid (DHA) and arachidonic acid (AA) are vital for brain and eye development. Specifically, normal visual and cognitive development is dependent on an adequate supply of DHA and AA in synapses and photoreceptors. Additionally, a lack of LC- PUFAs or an imbalance between I-3 and I-6 fatty acids, has been associated with a number of behavioral abnormalities, as well as neurological and psychiatric disorders in both children and adults, particularly attention-deficit hyperactivity (ADHD) and autism spectrm disorders, and unipolar and bipolar disorders. Pregnant mothers and their developing fetuses as well as young children who are impacted by malnutrition are particularly vulnerable because the staple foods they ingest have little or no preformed DHA or AA. Under such circumstances, the amount of LC-PUFAs found in circulation depends on that which can be synthesized from medium chain plant-based fatty acids (MC-FA). Studies from Dr. Chilton's laboratory in collaboration with Drs. Rasika Mathias and Kathleen Barnes at Johns Hopkins University School of Medicine have utilized DNA from the 52 populations described in the Human Diversity Panel and found that there are dramatic differences in populations with regard to those which contain alleles associated with efficient conversion of MC-FA to LC- PUFAs. Specifically, our data reveal that India sits geographically between populations to the east that have the alleles that facilitate the conversion of MC-FAs to LC-PUFAs and populations to the west of that have little capacity for conversion. Given, the high number of children exposed to malnutrition within India, it is vital to understand the distribution of alleles that impact LC-PUF synthesis throughout India. The objective of the current R-21 proposal is to initially establish a collaborative research program between Wake Forest University Health Sciences (WFUHS) and NITTE University/AB Shetty Memorial Institute of Dental Sciences (ABSMIDS)/K.S. Hegde Medical Academy (KSHEMA), Mangalore, India to put in place the infrastructure to analyze fatty acid nutritional status circulating fatty acid levels and allele frequencies in the FADS gene cluster in populations in the coastal city of Mangalore in the State of Karnataka in Southern India. Simultaneously in preparation for a more significant program for analyzing DNA and circulating fatty acids in large population centers of India (a subsequent R01), we will provide training mechanisms for investigators and PhD candidates from the Department of Biochemistry at NITTE University, KSHEMS and ABSMIDS, Mangalore, India in the areas of public health aspects of human genomics, nutrition and the consequences of impaired brain development, in the molecular and statistical techniques necessary to examine SNPs, genotypic/phenotypic associations and in methods involved in the analysis of food and blood lipids focusing on fatty acids. Together this will create a fertile local academic environment and a proven infrastructure needed to better understand how diverse Indian populations synthesize fats that are critical for brain and eye development. PUBLIC HEALTH RELEVANCE: Malnutrition is a major public health problem among infants and young children in Southeast Asia, especially India. We propose to train Indian scientist to use a combination of genetic and biochemical markers to understand how the diverse Indian populations make fats and the nutritional fatty acid requirements that are important in brain and eye development, in order combat fat malnutrition in a country that has 1/3 of the 150 million malnourished children in the world.

描述（由申请人提供）：长链多不饱和脂肪酸（LC-PUFA），例如二十二碳六烯酸（DHA）和花生四烯酸（AA）对于大脑和眼睛的发育至关重要。具体来说，正常的视觉和认知发育取决于突触和光感受器中 DHA 和 AA 的充足供应。此外，LC-PUFA 的缺乏或 I-3 和 I-6 脂肪酸之间的不平衡与儿童和成人的许多行为异常以及神经和精神疾病，特别是注意力缺陷多动有关（多动症）和自闭症谱系障碍，以及单相和双相情感障碍。怀孕的母亲及其发育中的胎儿以及受营养不良影响的幼儿特别容易受到伤害，因为他们摄入的主食中几乎没有或根本没有预先形成的 DHA 或 AA。在这种情况下，循环中发现的LC-PUFA的量取决于可以由中链植物性脂肪酸(MC-FA)合成的量。奇尔顿博士实验室与博士合作进行的研究。约翰·霍普金斯大学医学院的 Rasika Mathias 和 Kathleen Barnes 利用人类多样性小组中描述的 52 个人群的 DNA，发现含有与 MC-FA 有效转化为 MC-FA 相关的等位基因的人群存在显着差异。 LC-PUFA。具体来说，我们的数据显示，印度在地理上位于东部人口和西部人口之间，东部人口具有促进 MC-FA 转化为 LC-PUFA 的等位基因，而西部人口则几乎没有转化能力。鉴于印度境内有大量儿童营养不良，了解影响 LC-PUF 合成的等位基因在印度各地的分布至关重要。当前 R-21 提案的目标是初步建立一个维克森林大学健康科学 (WFUHS) 和 NITTE 大学/AB 谢蒂纪念牙科科学研究所 (ABSMIDS)/K.S. 之间的合作研究项目印度门格洛尔 Hegde 医学院 (KSHEMA) 将建立基础设施，分析印度南部卡纳塔克邦沿海城市门格洛尔人群中脂肪酸营养状况、循环脂肪酸水平和 FADS 基因簇中的等位基因频率。同时，为了准备在印度大型人口中心分析 DNA 和循环脂肪酸的更重要计划（随后的 R01），我们将为 NITTE 大学生物化学系、KSHEMS 和 ABSMIDS 的研究人员和博士生提供培训机制，印度门格洛尔在人类基因组学、营养和大脑发育受损后果的公共卫生方面，在检查单核苷酸多态性、基因型/表型关联和方法所需的分子和统计技术方面参与食品和血脂分析，重点关注脂肪酸。这将共同创造一个肥沃的当地学术环境和一个经过验证的基础设施，以更好地了解不同的印度人口如何合成对大脑和眼睛发育至关重要的脂肪。公共卫生相关性：营养不良是东南亚（尤其是印度）婴幼儿的一个主要公共卫生问题。我们建议培训印度科学家结合使用遗传和生化标记来了解不同印度人群如何制造脂肪以及对大脑和眼睛发育很重要的营养脂肪酸需求，以便在一个拥有 1 的国家对抗脂肪营养不良。世界上 1.5 亿营养不良儿童的 3 。