Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease

Sci Rep. 2018 Sep 4;8(1):13184. doi: 10.1038/s41598-018-31282-z.


We evaluated genetics of hyperuricemia and gout, their interaction with kidney function and medication intake in chronic kidney disease (CKD) patients. Genome-wide association studies (GWAS) of urate and gout were performed in 4941 CKD patients in the German Chronic Kidney Disease (GCKD) study. Effect estimates of 26 known urate-associated population-based single nucleotide polymorphisms (SNPs) were examined. Interactions of urate-associated variants with urate-altering medications and clinical characteristics of gout were evaluated. Genome-wide significant associations with serum urate and gout were identified for known loci at SLC2A9 and ABCG2, but not for novel loci. Effects of the 26 known SNPs were of similar magnitude in CKD patients compared to population-based individuals, except for SNPs at ABCG2 that showed greater effects in CKD. Gene-medication interactions were not significant when accounting for multiple testing. Associations with gout in specific joints were significant for SLC2A9 rs12498742 in wrists and midfoot joints. Known genetic variants in SLC2A9 and ABCG2 were associated with urate and gout in a CKD cohort, with effect sizes for ABCG2 significantly greater in CKD compared to the general population. CKD patients are at high risk of gout due to reduced kidney function, diuretics intake and genetic predisposition, making treatment to target challenging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • Aged
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glucose Transport Proteins, Facilitative / genetics
  • Gout / blood
  • Gout / complications*
  • Gout / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / genetics
  • Risk Factors
  • Uric Acid / blood*


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Glucose Transport Proteins, Facilitative
  • Neoplasm Proteins
  • SLC2A9 protein, human
  • Uric Acid