Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohortsBMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k3951 (Published 10 October 2018) Cite this as: BMJ 2018;363:k3951
- Tanya J Major, postdoctoral fellow1,
- Ruth K Topless, assistant research fellow1,
- Nicola Dalbeth, professor2,
- Tony R Merriman, professor1
- 1Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin 9054, New Zealand
- 2Department of Medicine, University of Auckland, Auckland, New Zealand
- Correspondence to: T R Merriman
- Accepted 28 August 2018
Objective To systematically test dietary components for association with serum urate levels and to evaluate the relative contributions of estimates of diet pattern and inherited genetic variants to population variance in serum urate levels.
Design Meta-analysis of cross sectional data from the United States.
Data sources Five cohort studies.
Review methods 16 760 individuals of European ancestry (8414 men and 8346 women) from the US were included in analyses. Eligible individuals were aged over 18, without kidney disease or gout, and not taking urate lowering or diuretic drugs. All participants had serum urate measurements, dietary survey data, information on potential confounders (sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, and menopausal status), and genome wide genotypes. The main outcome measures were average serum urate levels and variance in serum urate levels. β values (95% confidence intervals) and Bonferroni corrected P values from multivariable linear regression analyses, along with regression partial R2 values, were used to quantitate associations.
Results Seven foods were associated with raised serum urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb)) and eight foods were associated with reduced serum urate levels (eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and non-citrus fruits) in the male, female, or full cohorts. Three diet scores, constructed on the basis of healthy diet guidelines, were inversely associated with serum urate levels and a fourth, data driven diet pattern positively associated with raised serum urate levels, but each explained ≤0.3% of variance in serum urate. In comparison, 23.9% of variance in serum urate levels was explained by common, genome wide single nucleotide variation.
Conclusion In contrast with genetic contributions, diet explains very little variation in serum urate levels in the general population.
Contributors: TJM, ND, and TRM conceived the study. TJM and RKT managed and analysed the data. TJM and TRM wrote the manuscript. ND and RKT commented on drafts. All authors had full access to the data in the study and can take responsibility for the integrity of the data and accuracy of the data analysis. TRM is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: This work was supported by the Health Research Council of New Zealand and the University of Otago. The Sponsors had no role in designing, carrying out, and reporting the study.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: ND has received consulting fees, speaker fees, or grants from the following companies who have developed or marketed urate lowering drugs for management of gout: Takeda, Ardea Biosciences/AstraZeneca, Cymabay/Kowa, and Crealta/Horizon. TRM has received grants from Ardea Biosciences/AstraZeneca and Ironwood Pharmaceuticals.
Ethical approval: The ARIC, FHS, CHS, and CARDIA datasets were accessed through the Database of Genotype and Phenotype (www.ncbi.nlm.nih.gov/gap) via approval #834 and access was approved by the relevant Data Access Committees. All participants, including those in the NHANES III study, gave their written informed consent.
Data sharing: Code available from the corresponding author at firstname.lastname@example.org. Dataset also available provided that the requestor has the appropriate Database of Genotype and Phenotype approval.
The manuscript’s guarantor affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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