T. Flynn, R. Topless, T. R. Merriman
Affiliation(s):
Department of Biochemistry, University of Otago, Dunedin, Otago, New Zealand
Abstract: Gout is a consequence of an innate immune reaction to monosodium urate crystals deposited in joints. Acute gout attacks are commonly triggered by dietary factors, the most common of which have been associated with raised urate levels. However, individuals with gout often identify other foods as their gout triggers. The implementation of a hypothesis free diet wide association study (DWAS) could reveal foodstuffs that have not previously been associated with urate levels. 13,782 American Caucasian individuals from the Atherosclerosis Risk In Communities (n=7228), Coronary Artery Risk Development In (Young) Adults (n=1413), Cardiovascular Health (n=2101) and Framingham Heart (n=3040) studies were used to test for association between serum urate (μmolL-1) and 70 different foodstuffs (serves/week). All analyses were adjusted for sex, menopause status, age, BMI, average daily calorie intake and the first four eigenvectors from whole genome principal components analysis. Individuals with gout or kidney disease and those taking urate lowering medications or diuretics were excluded from analyses. Three quality control criteria were applied to the foodstuffs data to ensure reliable information was used. Six novel associations with a P < 0.0007 (Bonferroni multiple testing threshold) were found. Brown bread, peanut butter, eggs, non-citrus fruit and margarine all had urate lowering effects (β= −0.55; −0.93; −1.09; −0.35 and −0.36 μmolL-1 per extra serve per week respectively), whilst French-fried potatoes had a urate increasing effect (β= 2.30 μmolL-1 per extra serve per week). Additionally six known urate modifying foods, beer, cheese, shellfish, tea, skim milk and liquor (β= 1.48; −0.67; 5.11; 0.38; −0.92 and 1.63 μmolL-1 per extra serve per week) had P-values below the multiple testing threshold. Several other foods had associations trending toward significance (0.0007 < P < 0.05). This research represents the first diet wide association study in serum urate. The identification of novel and known urate modifying foods provides greater insight into how dietary factors can influence urate levels. Whilst we recognise several of these novel associations may be confounded by correlations with other foodstuffs, or represent differences in overall diet, this work is still an important first step toward a more inclusive understanding of dietary factors influencing urate levels and acute gout attacks.