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

Grant Number: 5R21TW008916-02
PI Name: Chilton
Project Title: Effect of FADS gene variants on fatty acid synthesis & brain development in India

Abstract: 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.

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