title: Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.
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 (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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.
authors.forename: Geetha
authors.initials: G
authors.lastname: Chittoor
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Nitesh R
authors.initials: NR
authors.lastname: Mehta
authors.affiliation: South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Laston
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Butte
authors.affiliation: 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.
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C570257:ZNF132 protein, human; C502773:ZNF446 protein, human; C000616852:ZNF584 protein, human; D014527:Uric Acid
keywords: Fractional excretion of uric acid; Genetic variation; Hispanic children; Uric acid clearance