title: Lack of gene-diuretic interactions on the risk of incident gout: the Nurses' Health Study and Health Professionals Follow-up Study.
abstract: BACKGROUND
  Diuretic-induced gout might occur only among those with a genetic predisposition to hyperuricaemia, as suggested by a recent study with 108 self-reported gout cases.
  
  
  METHODS
  We examined the role of urate genes on the risk of diuretic-induced incident gout in 6850 women from the Nurses' Health Study (NHS) and in 4223 men from the Health Professionals Follow-up Study (HPFS). Two published genetic risk scores (GRSs) were calculated using urate-associated single-nucleotide polymorphisms for 8 (GRS8) and 29 genes (GRS29).
  
  
  RESULTS
  Our analyses included 727 and 354 confirmed incident gout cases in HPFS and NHS, respectively. The multivariate relative risk (RR) for diuretic use was 2.20 and 1.69 among those with GRS8 < and ≥ the median (p for interaction=0.27). The corresponding RRs using GRS29 were 2.19 and 1.88 (p for interaction=0.40). The lack of interaction persisted in NHS (all p values >0.20) and in our analyses limited to those with hypertension in both cohorts. SLC22A11 (OAT4) showed a significant interaction only among women but in the opposite direction to the recent study.
  
  
  CONCLUSIONS
  In these large prospective studies, individuals with a genetic predisposition for hyperuricaemia are not at a higher risk of developing diuretic-induced gout than those without.
authors: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Ying
authors: Y
authors: Bao
authors: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Gary
authors: G
authors: Curhan
authors: University of Otago, Dunedin, New Zealand.
authors: Tony
authors: T
authors: Merriman
authors: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Robert
authors: R
authors: Plenge
authors: Harvard School of Public Health, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Peter
authors: P
authors: Kraft
authors: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Hyon K
authors: HK
authors: Choi
mesh_terms: D000328:Adult; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006073:Gout / Q000453:epidemiology* / Q000235:genetics*; D006282:Health Personnel; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D033461:Hyperuricemia / Q000453:epidemiology* / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009726:Nurses; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D004232:Diuretics
keywords: Epidemiology; Gene Polymorphism; Gout