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BMC Medical Genetics

, 18:6

Genetic epidemiology and genetic associations

Abstract

BackgroundReduced 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.

MethodsWe 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.

ResultsAll renal urate excretion measures were significantly heritable p <2 × 10 and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10. We observed a strong association p < 8 × 10 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, MAFs: 0.28–0.31.

ConclusionFor 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.

KeywordsUric acid clearance Genetic variation Fractional excretion of uric acid Hispanic children AbbreviationsABCG2ATP-binding cassette ABC, subfamily G, member 2

CrClCreatinine clearance

EUAGFExcretion of uric acid per volume of glomerular filtration

FEUAFractional excretion of uric acid

GCKRGlucokinase regulator

GLUAGlomerular load of uric acid

GWASGenome-wide association study

IGF1RInsulin like growth factor 1 receptor

SLC2A9Solute carrier family 2, member 9

SrCrSerum creatinine

SUASerum uric acid

UAClUric acid clearance

URAT-1Uric acid transporter-1 protein

UrCrUrinary creatinine

UrUAUrinary uric acid

UrUA-UrCrUrinary uric acid to urinary creatinine ratio

VFSViva La Familia Study

ZNFZinc Finger Proteins

Electronic supplementary materialThe online version of this article doi:10.1186-s12881-016-0366-3 contains supplementary material, which is available to authorized users.

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Autor: Geetha Chittoor - Karin Haack - Nitesh R. Mehta - Sandra Laston - Shelley A. Cole - Anthony G. Comuzzie - Nancy F. Butt

Fuente: https://link.springer.com/



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