Abstract
BackgroundReduced renal clearance of uric acid is a major contributor to hyperuricemia. The aim of this study was to examine clinical and genetic variables associated with fractional excretion of uric acid (FEUA).MethodsParticipants (with and without gout) in the Genetics of Gout in Aotearoa study with available genotyping and FEUA data were included (n = 1713). Ten FEUA-associated loci detected within a genome-wide association study for serum urate in a European population were analysed. A polygenic score for FEUA was calculated in each ancestry group to model the cumulative effects of the genetic variants on FEUA. Associations between FEUA and both clinical variables and polygenic score were tested using linear regression models.ResultsThe mean (SD) FEUA was 5.13 (2.70) % in Eastern Polynesian participants, 4.70 (5.89) % in Western Polynesian participants, and 5.89 (2.73) % in New Zealand European participants. Although association with FEUA was observed for SLC2A9 rs11942223 in New Zealand European participants (P = 2.39 × 10− 8), this association was not observed in Eastern or Western Polynesian participants. The polygenic score was positively associated with FEUA in all ancestry groups. In New Zealand European participants, body mass index, diuretic use, polygenic score, and male sex were associated with FEUA and explained 22% of FEUA variance in the regression model. In Eastern and Western Polynesian participants, the tested variables explained 10% and 4% of FEUA variance respectively.ConclusionsBoth clinical and genetic variables contribute to renal clearance of uric acid. SLC2A9 exerts effects on FEUA variance in people of European ancestry, but not in those of Polynesian ancestry. There is a large unexplained variance in FEUA, particularly in people of Polynesian ancestry.
Highlights
Reduced renal clearance of uric acid is a major contributor to hyperuricemia
There was no significant difference in fractional excretion of uric acid (FEUA) between Eastern and Western Polynesian participants (Tukey post hoc P = 0.08)
This study has identified independent clinical and genetic variables that contribute to fractional excretion of uric acid
Summary
The aim of this study was to examine clinical and genetic variables associated with fractional excretion of uric acid (FEUA). Renal under-excretion of uric acid is the dominant cause of hyperuricaemia in 80–90% of people with gout [1, 2]. A number of clinical variables associate with the renal handling of uric acid, including body mass index (BMI) [3], kidney disease [4] and diuretic use [5]. These variables are important contributors to the development of hyperuricaemia and gout. In the Global Urate Genetics Consortium genome-wide association study (GWAS) for serum urate, Köttgen et al [9] identified ten serum urate-associated single
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