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


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.
['Chittoor|Geetha|G|', 'Haack|Karin|K|', 'Mehta|Nitesh R|NR|', 'Laston|Sandra|S|', 'Cole|Shelley A|SA|', 'Comuzzie|Anthony G|AG|', 'Butte|Nancy F|NF|', 'Voruganti|V Saroja|VS|']
D000293:Adolescent D015415:Biomarkers D002648:Child D004268:DNA-Binding Proteins D005260:Female D014644:Genetic Variation D055106:Genome-Wide Association Study D006801:Humans D008297:Male D020641:Polymorphism, Single Nucleotide D012097:Repressor Proteins D014157:Transcription Factors D014527:Uric Acid
Genetic variation Hispanic children Uric acid clearance Fractional excretion of uric acid