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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #342589
Title: Genetic variation underlying renal uric acid excretion in Hispanic children: The Viva La Familia Study

Author
item CHITTOOR, GEETHA - University Of North Carolina
item HAACK, KARIN - Texas Biomedical Institute
item MEHTA, NITESH - Children'S Nutrition Research Center (CNRC)
item LASTON, SANDRA - University Of Texas Rio Grande Valley
item COLE, SHELLEY - Texas Biomedical Institute
item COMUZZIE, ANTHONY - Texas Biomedical Institute
item BUTTE, NANCY - Children'S Nutrition Research Center (CNRC)
item VORUGANTI, V - University Of North Carolina

Submitted to: BMC Medical Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2016
Publication Date: 1/17/2017
Citation: Chittoor, G., Haack, K., Mehta, N.R., Laston, S., Cole, S.A., Comuzzie, A.G., Butte, N.F., Voruganti, V.S. 2017. Genetic variation underlying renal uric acid excretion in Hispanic children: The Viva La Familia Study. BMC Medical Genetics. 18(1):6.

Interpretive Summary: Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia which is associated with chronic kidney disease and cardiovascular disease. In this study, genetic factors that influence the excretion of uric acid in 768 Hispanic children of the Viva La Familia Study was investigated. A genome-wide association analysis was performed on 24-h urinary excretion indices including urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid. The principal finding were uric acid clearance was related to a single nucleotide polymorphism (SNP) in the gene zinc finger protein 446 (ZNF446) and suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132. For the first time, we showed the importance of a region on chromosome 19 involved in the regulation of renal urate excretion in Hispanic children.

Technical Abstract: 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. 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. All renal urate excretion measures were significantly heritable (p <2'×'10-6) 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 <1'×'10-6, MAFs: 0.28-0.31). 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.