RT Journal Article
SR Electronic
T1 Do serum urate-associated genetic variants influence gout risk in people on diuretics? Analysis of the UK Biobank
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.191005
DO 10.3899/jrheum.191005
A1 Ravi K.  Narang
A1 Greg Gamble
A1 Amanda J.  Phipps-Green
A1 Ruth Topless
A1 Murray Cadzow
A1 Lisa K.  Stamp
A1 Tony R.  Merriman
A1 Nicola Dalbeth
YR 2020
UL http://www.jrheum.org/content/early/2020/01/27/jrheum.191005.abstract
AB Objective The aim of this study was to determine whether serum urate-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 serum urate-associated single nucleotide polymorphisms (SNPs) 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 SNPs by logistic regression adjusting for relevant confounders. Results After adjustment, use of a loop diuretic was positively associated with prevalent gout (OR 2.34 [2.08-2.63]), but thiazide diuretics were inversely associated with prevalent gout (OR 0.60 [0.55-0.66]). Compared with a lower GRS (< mean), a higher GRS (≥ mean) was positively associated with gout in those not on diuretics (OR 2.63 [2.49-2.79]), in those on loop diuretics (OR 2.04 [1.65-2.53]), in those on thiazide diuretics (OR 2.70 [2.26-3.23]), and in those on thiazide-like diuretics (OR 2.11 [1.37-3.25]). No non-additive gene-diuretic interactions were observed. Conclusion In people on diuretics, serum urate-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 genetic variants can play an important role in gout susceptibility in the presence of other risk factors.