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Research ArticleGout

Do Serum Urate–associated Genetic Variants Influence Gout Risk in People Taking Diuretics? Analysis of the UK Biobank

Ravi K. Narang, Greg Gamble, Amanda J. Phipps-Green, Ruth Topless, Murray Cadzow, Lisa K. Stamp, Tony R. Merriman and Nicola Dalbeth
The Journal of Rheumatology November 2020, 47 (11) 1704-1711; DOI: https://doi.org/10.3899/jrheum.191005
Ravi K. Narang
1R.K. Narang, MBChB, G. Gamble, MSc, N. Dalbeth, FRACP, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland;
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Greg Gamble
1R.K. Narang, MBChB, G. Gamble, MSc, N. Dalbeth, FRACP, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland;
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Amanda J. Phipps-Green
2A.J. Phipps-Green, MSc, R. Topless, BSc, M. Cadzow, PhD, T.R. Merriman, PhD, Department of Biochemistry, University of Otago, Dunedin;
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Ruth Topless
2A.J. Phipps-Green, MSc, R. Topless, BSc, M. Cadzow, PhD, T.R. Merriman, PhD, Department of Biochemistry, University of Otago, Dunedin;
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Murray Cadzow
2A.J. Phipps-Green, MSc, R. Topless, BSc, M. Cadzow, PhD, T.R. Merriman, PhD, Department of Biochemistry, University of Otago, Dunedin;
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  • ORCID record for Murray Cadzow
Lisa K. Stamp
3L.K. Stamp, Department of Medicine, University of Otago, Christchurch, New Zealand.
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Tony R. Merriman
2A.J. Phipps-Green, MSc, R. Topless, BSc, M. Cadzow, PhD, T.R. Merriman, PhD, Department of Biochemistry, University of Otago, Dunedin;
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Nicola Dalbeth
1R.K. Narang, MBChB, G. Gamble, MSc, N. Dalbeth, FRACP, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland;
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  • For correspondence: n.dalbeth@auckland.ac.nz
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Abstract

Objective The aim of this study was to determine whether serum urate (SU)–associated genetic variants differ in their influence on gout risk in people taking a diuretic compared to those not taking a diuretic.

Methods This research was conducted using the UK Biobank Resource (n = 359,876). Ten SU-associated single-nucleotide polymorphisms (SNP) were tested for their association with gout according to diuretic use. Gene-diuretic interactions for gout association were tested using a genetic risk score (GRS) and individual SNP by logistic regression adjusting for relevant confounders.

Results After adjustment, use of a loop diuretic was positively associated with prevalent gout (OR 2.34, 95% CI 2.08–2.63), but thiazide diuretics were inversely associated with prevalent gout (OR 0.60, 95% CI 0.55–0.66). Compared with a lower GRS (< mean), a higher GRS (≥ mean) was positively associated with gout in those not taking diuretics (OR 2.63, 2.49–2.79), in those taking loop diuretics (OR 2.04, 95% CI 1.65–2.53), in those taking thiazide diuretics (OR 2.70, 2.26–3.23), and in those taking thiazide-like diuretics (OR 2.11, 95% CI 1.37–3.25). No nonadditive gene-diuretic interactions were observed.

Conclusion In people taking diuretics, SU-associated genetic variants contribute strongly to gout risk, with a similar effect to that observed in those not taking a diuretic. These findings suggest that the contribution of genetic variants is not restricted to people with “primary” gout, and that genetic variants can play an important role in gout susceptibility in the presence of other risk factors.

Key Indexing Terms:
  • diuretics
  • genetics
  • gout
  • hyperuricemia

Footnotes

  • TRM has received consulting fees or grants from Ardea Biosciences and AstraZeneca. ND has received consulting fees, speaker fees, or grants from AstraZeneca, Dyve Bio, Hengrui, Pfizer, Jannsen, AbbVie, and Horizon.

  • This work was supported by the Health Research Council of New Zealand (grant number 14-527).

  • Accepted for publication January 16, 2020.
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Do Serum Urate–associated Genetic Variants Influence Gout Risk in People Taking Diuretics? Analysis of the UK Biobank
Ravi K. Narang, Greg Gamble, Amanda J. Phipps-Green, Ruth Topless, Murray Cadzow, Lisa K. Stamp, Tony R. Merriman, Nicola Dalbeth
The Journal of Rheumatology Nov 2020, 47 (11) 1704-1711; DOI: 10.3899/jrheum.191005

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Do Serum Urate–associated Genetic Variants Influence Gout Risk in People Taking Diuretics? Analysis of the UK Biobank
Ravi K. Narang, Greg Gamble, Amanda J. Phipps-Green, Ruth Topless, Murray Cadzow, Lisa K. Stamp, Tony R. Merriman, Nicola Dalbeth
The Journal of Rheumatology Nov 2020, 47 (11) 1704-1711; DOI: 10.3899/jrheum.191005
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Keywords

diuretics
GENETICS
GOUT
HYPERURICEMIA

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