title: Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.
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.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Reynolds
authors.affiliation: Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Vazquez
authors.affiliation: Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
authors.forename: Vinodh
authors.initials: V
authors.lastname: Srinivasasainagendra
authors.affiliation: Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA.
authors.forename: S Louis
authors.initials: SL
authors.lastname: Bridges
authors.affiliation: Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA. Jasvinder.md@gmail.com.
authors.forename: Jasvinder A
authors.initials: JA
authors.lastname: Singh
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015897:Comorbidity; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D014527:Uric Acid
keywords: Genetic urate score; Gout comorbidities; Metabolic syndrome; Obesity