Background/Purpose: We aim to assess the association of 8 serum urate SNPs and BMI and their interactions with incident gout in a population-based cohort study.

Methods: We used the Framingham Study including subject from the Original and the Offspring cohort (N=4,967). We assessed the effect of 8 SNPs in the recently described genetic urate score on incident gout. Subjects were genotyped with Affy500K platform, and two of the SNPs associated to gout rs1165196 and rs1106766 were present in that platform. The SNPs rs1967017, rs780093, rs13129697, rs2199936, rs675209 and rs2078267 were not present in the Affy SNP array, thus we imputed them with IMPUTE2. BMI was taken at the time of gout or, at the time of censoring if the subject is healthy or died without gout. We fitted logistic regression models to assess the associations. Estimated effects in the liability scale, odd ratios, and p-values are reported for all SNPs, covariates, and interactions. 408 patients had incident gout (74% males), with 169 from the FHS original cohort and 293 from the Offspring cohort.

Results: In a model with main effects of BMI and SNPs, three of eight SNPs and BMI were significantly associated with incident gout (p<=0.008 for all). Zero SNPs showed significant main effects on gout in the model that adjusted for all BMI*SNP interaction terms. However, BMI remained significant (p=0.003) and the rs2199936*BMI interaction was nearly significant (p=0.06). Gender and duration of follow-up were also significant predictors (p<=0.009) in all models.

Conclusion: SNPs known to predict urate levels moderated the association of BMI with gout, suggesting the possibility that the extent to which BMI increases the risk for got may depend on a person’s a priori genetic risk for high urate levels.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-bmi-8-snps-reported-to-be-related-to-gout-phenotype-and-their-interaction-in-gout-incidence-in-framingham-heart-study/