Serum urate (SU)-associated genetic variants contribute strongly to gout risk among patients taking diuretics, according to a recent study.

“This suggests that the contribution of genetic variants is not restricted to people with primary gout and that it can play an important role in gout susceptibility in the presence of other risk factors,” a team led by Nicola Dalbeth, MD, MBChB, of the University of Auckland in Auckland, New Zealand, concluded in a paper published in the Journal of Rheumatology.

Using the UK Biobank Resource, the investigators examined the association between 10 SU-associated single-nucleotide polymorphisms (SNP) and gout according to diuretic use among 359,517 individuals for whom genome-wide genotypes were available. Dr Dalbeth and her colleagues calculated a genetic risk score (GRS) to model the cumulative effects of an individual’s risk for the 10 variants. For each of the SU-associated SNP, the investigators calculated the allelic odds ratios (ORs) to determine gout risk, which was adjusted for age, sex, and body mass index. They converted the ORs into logarithmic values. For each individual, they multiplied the logarithmic values by the number of urate-raising alleles and summed them into a weight GRS. Higher scores indicated a greater genetic predisposition for gout, they noted.

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In adjusted analyses, a loop diuretic was significantly associated with 2.3-fold increased odds of prevalent gout, whereas thiazide diuretic use was significantly associated with 40% decreased odds of prevalent gout, Dr Dalbeth and colleagues reported. Compared with a lower GRS (below the mean value), a higher score (the mean value or higher) was significantly associated with 2.6-fold increased odds of gout among individuals not taking diuretics, 2.0-fold increased odds among those taking loop diuretics, and 2.7-fold increased odds among those taking thiazide diuretics.

The 359,517 individuals in the study included 330,165 individuals (91.8%) who did not take diuretics (controls) and 29,352 (8.2%) diuretic users. Of those taking diuretics, 23,623 (80.5%) were thiazide diuretic users, 3728 (12.7%) took loop diuretics, and 2001 (6.8%) used thiazide-like diuretics. A total of 7324 individuals had gout. Gout was present in 462 (12.4%) loop diuretic users, 615 (2.6%) thiazide diuretic users, 102 (5.1%) thiazide-like diuretic users, and 6145 (1.9%) nondiuretic users.

In the no-diuretic group, the mean GRS was 1.30 among individuals with gout compared with 1.15 for controls. Among patients taking loop diuretics and thiazide diuretics, the mean scores were 1.25 and 1.28, respectively, among gout sufferers compared with 1.14 and 1.14, respectively, among controls. In the group taking thiazide-like diuretics, the individuals with gout had a mean score of 1.29, whereas controls had a mean score of 1.14.


Narang RK, Gamble G, Phipps-Green AJ, et al. Do serum urate-associated genetic variants influence gout risk in people taking diuretics? Analysis of the UK Biobank. J Rheumatol. 2020;47:1704-1711. doi:10.3899/jrheum.191005