Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Chittoor, Geetha; Haack, Karin; Mehta, Nitesh; Laston, Sandra; Cole, Shelley; Comuzzie, Anthony; Butte, Nancy; Voruganti, V.
• Is Part Of: BMC medical genetics. Volume 18:Issue 1(2017)
• Page Start: 1
• Page End: 8
• Publication Date: 2017-12
• Subjects: Uric acid clearance -- Genetic variation -- Fractional excretion of uric acid -- Hispanic children; Medical genetics -- Periodicals; 616.04205
• DOI: 10.1186/s12881-016-0366-3
• Languages: English
• ISSNs: 1471-2350

Abstract

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 atp <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 inZNF324, ZNF584, andZNF132 (in a 72 kb region of 19q13;p <1 × 10−6, MAFs: 0.28–0.31). 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.