Obesity Associated With Increased Risk for Gout, Higher Serum Urate Concentrations

Overall obesity measured by body mass index (BMI) is associated with an increased risk for gout and with higher serum urate concentrations, according to the results of a Mendelian randomization study published in Rheumatology.

The investigators sought to explore whether overall obesity, as measured by BMI, and abdominal obesity, as measured by waist-to-hip ratio (WHR) adjusted for BMI, are linked to an elevated risk for gout and serum urate levels. Single-nucleotide polymorphisms (SNPs) associated with BMI (n=97) and WHR adjusted for BMI (n=49) were evaluated with respect to their association with risk for gout in 2115 patients with gout and 67,259 control patients, and with serum urate concentrations in 110,347 individuals from the Global Urate Genetics Consortium.

Results of the analysis showed that genetically predicted BMI was positively associated with the risk for gout. With the use of data from all 97 BMI-associated SNPs, the odds ratio of gout per 1 standard deviation (approximately 4.6 kg/m²) increase in genetically predicted BMI was 2.24 (95% CI, 1.70-2.95; P =8.4 × 10⁻⁹), without heterogeneity, among SNPs (P =.87). In contrast, genetically predicted WHR adjusted for BMI was not associated with gout.

In addition, BMI was positively associated with serum urate concentrations, with a 0.30 mg/dL (95% CI, 0.25-0.35; P =1.6 × 10⁻³⁶) higher serum urate level per standard deviation increase in genetically predicted BMI. No association was demonstrated between WHR adjusted for BMI and serum urate level (0.05 mg/dL; 95% CI, −0.02 to 0.11; P =.17).

The study provides evidence that higher BMI, but not WHR adjusted for BMI, is causally linked to risk for gout independent of other risk factors and is associated with higher serum urate concentrations. Each standard deviation increase in genetically predicted BMI was associated with a >2-fold elevated risk for gout and a 0.30 mg/dL increase in serum urate concentrations.

The investigators noted that as in any Mendelian randomization study, the likelihood that pleiotropy may have affected the results cannot be totally dismissed. Nonetheless, the genetic link between BMI and risk for gout was similar in sensitivity analyses, with no evidence of pleiotropy observed. The researchers note that they could not evaluate the associations of adiposity with gout and serum urate concentrations separately for men and women, with potentially different accumulations of fat in different body locations.

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Reference

Larsson SC, Burgess S, Michaëlsson K. Genetic association between adiposity and gout: a Mendelian randomization study [published online August 4, 2018]. Rheumatology (Oxford). doi: 10.1093/rheumatology/key229