Journal Articles

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

February 09, 2017

Chittoor G, Haack K, Mehta NR, Laston S, Cole SA, Comuzzie AG, Butte NF, Voruganti VS (2017). Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study. BMC Medical Genetics. 18(1):6.

Author Affiliations

Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.
Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA. saroja@unc.edu.

Abstract

BACKGROUND:
Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study.
METHODS:
We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members.
RESULTS:
All renal urate excretion measures were significantly heritable and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p < 1 × 10-7. We observed a strong association (p < 8 × 10-8) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.
CONCLUSION:
For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

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