title: A urate gene-by-diuretic interaction and gout risk in participants with hypertension: results from the ARIC study.
abstract: OBJECTIVE
  To test for a urate gene-by-diuretic interaction on incident gout.
  
  
  METHODS
  The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median.
  
  
  RESULTS
  Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney.
  
  
  CONCLUSIONS
  Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St, Suite B-319, Baltimore, MD 21287, USA. mmcadams@jhsph.edu
authors: Mara A
authors: MA
authors: McAdams-DeMarco
authors: Janet W
authors: JW
authors: Maynard
authors: Alan N
authors: AN
authors: Baer
authors: Linda W
authors: LW
authors: Kao
authors: Anna
authors: A
authors: Kottgen
authors: Josef
authors: J
authors: Coresh
mesh_terms: D016208:Databases, Factual / Q000706:statistics & numerical data; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D033461:Hyperuricemia / Q000453:epidemiology / Q000235:genetics; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood
chemical_list: D004232:Diuretics; D051246:Glucose Transport Proteins, Facilitative; D029362:Organic Anion Transporters, Sodium-Independent; C427207:SLC22A11 protein, human; C411811:SLC2A9 protein, human; D014527:Uric Acid