Ying Bao1, Gary Curhan2, Tony Merriman3, Robert Plenge4, Peter Kraft5, Hyon K Choi6. 1. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. 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. 3. University of Otago, Dunedin, New Zealand. 4. Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 5. Harvard School of Public Health, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 6. 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.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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