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. 2016 Feb;36(2):263-70.
doi: 10.1007/s00296-015-3364-4. Epub 2015 Oct 1.

Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index

Richard J Reynolds  1 , Ana I Vazquez  2 , Vinodh Srinivasasainagendra  2 , Yann C Klimentidis  3 , S Louis Bridges Jr  1 , David B Allison  4 , Jasvinder A Singh  5
Affiliations

Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index

Richard J Reynolds et al. Rheumatol Int. 2016 Feb.

Abstract

We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk of incident gout. We measured the incidence of gout and associated comorbidities using the original and offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the eight SNPs. Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P = 6.12E-03). We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk of gout may involve complex interplay between genes and environment.

Keywords: Genetic urate score; Gout comorbidities; Metabolic syndrome; Obesity.

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Figures

Figure 1
Figure 1
Six generalized linear models to test the association of genetic and environmental covariates with gout incidence. *excluding intercept. ** GRS calculated as the sum of reference (gout increasing) alleles across the eight serum urate associated loci.
Figure 1
Figure 1
Six generalized linear models to test the association of genetic and environmental covariates with gout incidence. *excluding intercept. ** GRS calculated as the sum of reference (gout increasing) alleles across the eight serum urate associated loci.
Figure 2
Figure 2
Renal disease and the serum urate associated loci, INHBC has a non-additive association with incident gout. The interaction plot shows the minor allele frequency of the INHBC SNP (rs1106766) by category of renal disease and incident gout.
See this image and copyright information in PMC

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