Author
VORUGANTI, V - University Of North Carolina | |
LASTON, SANDRA - Texas Biomedical Institute | |
HAACK, KARIN - Texas Biomedical Institute | |
MEHTA, NITESH - Children'S Nutrition Research Center (CNRC) | |
COLE, SHELLEY - Texas Biomedical Institute | |
BUTTE, NANCY - Children'S Nutrition Research Center (CNRC) | |
COMUZZIE, ANTHONY - Texas Biomedical Institute |
Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/22/2014 Publication Date: 1/28/2015 Citation: Voruganti, V.S., Laston, S., Haack, K., Mehta, N.R., Cole, S.A., Butte, N.F., Comuzzie, A.G. 2015. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: The Viva La Familia Study. American Journal of Clinical Nutrition. 101:725-732. Interpretive Summary: Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. The aim of this study was to determine if serum uric acid levels in Hispanic children is under genetic influence and whether variation in serum uric acid is partially accounted for by polymorphisms in the renal transport gene, SLC2A9. A study was conducted using 1.1 million genetic markers in 815 Hispanic children of the Viva La Familia Study. Our results showed that serum uric acid levels are heritable and associated with genetic variants in SLC2A9 in Hispanic children. Serum uric acid and weight status appear to be under shared genetic control. Similar to adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children. This provides a new potential target for interventions. Technical Abstract: Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children. The aim was to investigate whether variation in serum uric acid is under genetic influence and whether the association with SLC2A9 polymorphisms generalizes to Hispanic children of the Viva La Familia Study. We conducted a genomewide association study with 1.1 million genetic markers in 815 children. We found serum uric acid to be significantly heritable [h2 +/SD = 0.45 +/ 0.08, P = 5.8 x 10-11] and associated with SLC2A9 variants (P values between 10-16 and 10-7). Several of the significantly associated polymorphisms were previously identified in studies in adults. We also found positive genetic correlations between serum uric acid and BMI z score (pG = 0.45, P = 0.002), percentage of body fat (pG = 0.28, P = 0.04), fat mass (pG = 0.34, P = 0.02), waist circumference (pG = 0.42, P = 0.003), and waist-to- height ratio (pG = 0.46, P = 0.001). Our results show that variation in serum uric acid in Hispanic children is under considerable genetic influence and is associated with obesity-related phenotypes. As in adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children. |