Background/Purpose: Hyperuricaemia (elevated serum urate) is a central risk factor for gout, an acute inflammatory form of arthritis. The balance between the hepatic production of urate and the intestinal / renal urate excretion pathways determines an individual’s serum urate levels and this balance can be modified by both genetic and environmental factors. This study aimed to evaluate the relative contributions of estimates of diet quality and inherited genetic variants in determining serum urate levels.

Methods: 16,760 American European individuals (8,414 men, 8,346 women) were used to test for associations between serum urate (µmol/L) and four composite dietary scores or a genetic risk score, adjusting for sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, menopausal status, and genome-wide principal component vectors. Genetic heritability of serum urate in these individuals was also assessed.

Results: Three diet quality scores, constructed based on healthy diet guidelines (Healthy-Eating Pyramid, DASH Diet, and Mediterranean Diet), were inversely associated with serum urate (β (in μmol/L) = -0.72, P = 1.12×10^-6; β = -0.73, P = 3.1×10^-10; β = -0.38, P = 2.9×10^-4, respectively) and a fourth, data-driven diet quality score associated with raised serum urate (β = 0.59, P = 2.3×10^-8). However, each explained ≤ 0.28% of the cohort variance in serum urate. In comparison, a weighted serum urate genetic risk score, constructed from 30 variants previously associated with serum urate in Europeans (Köttgen et al. 2013), associated with raised serum urate (β = 0.99, P = 2.2×10^-231) and explained 7.9% of the serum urate variance within the cohort. A genome-wide estimate of serum urate heritability explained 23.9% (P < 1.0×10^-16) of the cohort variance in serum urate.

Conclusion: This study has identified an association between estimates of healthier dietary habits and reduced urate in people of European ancestry and suggests, in contrast to genetic contributions, diet explains very little variation in serum urate levels. Our results are important in demonstrating the relative contributions of overall diet and inherited genetic factors to the population variance of serum urate levels and challenge widely held community perceptions that hyperuricaemia is primarily caused by diet. This study directly shows, for the first time, that genetic variants have a much greater contribution to population-wide variance in hyperuricaemia than dietary habits.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/estimates-of-diet-quality-explain-less-variability-in-serum-urate-levels-than-genetic-factors/