A Genetic Answer

Le Bonheur researcher studies a fatty acid metabolism gene and its ties to racial disparity in health outcomes and pediatric obesity

A Le Bonheur researcher has found a genetic link that may explain differences in metabolic health and body composition in children with severe obesity. Genes may influence obesity-related health complications that disproportionately affect African-American children.

The research, developed by Exercise Physiologist Webb Smith, PhD, and his lead collaborators at the University of Tennessee Health Science Center (UTHSC), Ryan Yates, Pharm-D, PhD, and Joan Han, MD, was presented in August at the American Gastroenterological Association’s James Freston Conference.

Smith works with severely obese children every day at Le Bonheur Children’s Healthy Lifestyles Clinic – a multi-disciplinary weight management clinic. Throughout his work with these children, he noted that this clinic was unique in that it was comprised of primarily African-American patients who were reported to have worse outcomes when compared to Caucasian patients.

The Modern Western Diet (MWD) is high in refined sugar, fat and carbohydrates according to the Offices of Disease Prevention and Health Promotion. While many people eat this diet, not all develop the health complications related to the MWD such as obesity, heart disease and diabetes. Smith and his team worked to identify genetic factors that may explain why patients respond differently to unhealthy dietary patterns.

The gene at the center of Smith’s study is FADS1 (fatty acid desaturase 1), which determines how an individual metabolizes polyunsaturated fatty acids (PUFA) according to GeneCards Human Gene Database. The study compared the FADS1 gene variants and their associations with metabolic health and body composition in children with severe obesity.

Smith found that those with the GG genotype of FADS1 were high PUFA metabolizers, which results in increased arachidonic acid levels. High arachidonic acid levels are a known contributor to chronic inflammation and are commonly associated with obesity. African-Americans had an increased frequency of this GG genotype.

“This study sought to investigate why obesity-related health complications disproportionately affect African-Americans,” said Smith. “Both diet and genetic risk may be important factors.”

The project examined data for 320 children to show the effect of the GG genotype on a child’s health. After stratifying by race and adjusting for age and sex, body fat percentage and visceral fat area were significantly higher in individuals with the GG genotype.

“Our research showed the problematic effects of the GG genotype,” said Smith. “This genotype is related to higher body fat percentage and a more unfavorable distribution of that fat.”

Smith’s  team reported that African-American children had a larger percentage of the GG genotype at 95.8 percent compared to 75.0 percent of the Caucasian children. In turn, he saw a significant difference in the proportion of African-American patients diagnosed with additional health issues such as elevated triglyceride, abnormal liver function and elevated LDL (low-density lipoprotein).

Smith concluded that the FADS1 genotype is associated with unfavorable body composition and high-risk body fat distribution patterns, and that there is also an association between the FADS1 genotype and metabolic health in African- American patients.

“These results are significant because this particular risk allele is more likely to impact African-American children and may explain part of the elevated risk for metabolic health complications,” said Smith.

Smith and his team plan to conduct further studies across the body weight spectrum to further understand the significance of the FADS1 gene in obesity.

The results of this study have potential implications for medical practice with severely obese children, Smith said. This genotype also can provide direction for precision nutrition counseling. For example, those with the GG genotype would need to limit overall PUFA intake and focus heavily on balancing omega 6 and omega 3 intakes.

“This data may be useful for determining how to screen and care for patients,” said Smith. “We can better understand the risk of developing metabolic complications and facilitate early treatment.