Study on genetic capacity of diverse populations to make critical PUFAs

Published on November 8, 2012 at 6:52 AM · No Comments

World-renowned scientists are taking what they've learned from their multicenter research collaboration studying the health impact of fatty acids on diverse populations to set up a genetics center in India.

Wake Forest Baptist Medical Center researchers Floyd H. "Ski" Chilton, Ph.D., and Avinash K. "Avi" Shetty, M.D., are studying genetic differences in populations related to how they convert certain dietary fats known as polyunsaturated fatty acids (PUFAs).

"Given that one third of all severely malnourished children are in India, it is vital to understand the distribution of gene variants that impact long-chain PUFA synthesis in this country," Chilton said. "We're particularly interested in PUFAs because they are so critical for brain and immune development early in life."

With new grant funding from the National Institutes of Health, they will take their research to the coastal city of Mangalore in the state of Karnataka in Southern India to study its diverse populations and their genetic capacity to make PUFAs that are critical for brain, eye and immune system development.

The collaboration brings together Wake Forest Baptist, the Johns Hopkins School of Medicine and the NITTE University/K.S. Hegde Medical Academy/AB Shetty Memorial Institute of Dental Sciences in Mangalore. Chilton, a professor of physiology and pharmacology and director of the Center for Botanical Lipids and Inflammatory Disease Prevention at Wake Forest Baptist, and Shetty, a professor of pediatrics, have a long collaborative history with Rasika S. Mathias, ScD., and Kathleen Barnes, Ph.D., of Johns Hopkins.

The researchers have published numerous papers over the last several years highlighting how variations within a set of genes, known as the FADS gene cluster on chromosome 11, impact PUFA metabolism in African and European ancestry populations as well as other populations around the world. Specifically, they have found that genetic variation within the FADS cluster has undergone intense natural selection and thereby led to different frequencies in the differing populations. Given these observations, the team is performing ongoing research to understand whether the dramatic increase in dietary omega-6 PUFAs found in the modern "western" diet harms certain populations more than others.

Chilton said he envisions a day when malnutrition could be optimally addressed by knowing how different populations utilize dietary components such as PUFAs. "It may be that one malnourished population requires one set of nutrients and another a different set of nutrients," he said.

Long-chain PUFAs 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, said Chilton, a lack of LCPUFAs or an imbalance between omega 3 and omega 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 spectrum disorders, as well as unipolar and bipolar disorders.

This new effort is being supported with a two-year, $200,000 grant from The John E. Fogarty International Center for Advanced Study in the Health Sciences, part of The National Institutes of Health. The center supports basic, clinical and applied research and training for U.S. and foreign investigators working in the developing world. Since its formation more than 40 years ago, Fogarty has served as a bridge between NIH and the greater global health community-facilitating exchanges among investigators, providing training opportunities and supporting promising research initiatives in developing countries. Over four decades, about 5,000 scientists worldwide have received significant research training through Fogarty funding programs. The funding will be used to set up training mechanisms for investigators and Ph.D. candidates from the three partnering institutions, which are all making in-kind contributions of staff, labs and equipment. The long-term objective, said Mathias, is to create the technical and intellectual infrastructure to carry out a larger project to analyze DNA and circulating fatty acids in major population centers in India.

"This is the first step to help us 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," Chilton said. "Our ultimate hope and dream is to one day create therapeutic foods based on genetic backgrounds of different populations to treat malnutrition."

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