Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Diuretics, particularly thiazide and loop diuretics, increase the risk of gout, likely through urate transporters (e.g., OAT4) and volume depletion promoting urate reabsorption. As the prevalence of hypertension is remarkably high in gout patients (74% in the US general population), diuretic use is commonly encountered in gout care as a first line anti-hypertensive agent. A recent analysis based on 108 self-reported incident cases of gout in the Atherosclerosis Risk in Communities (ARIC) Study has reported that diuretic-induced gout occurs only among those with a genetic predisposition to hyperuricemia (Ann Rheum Dis 2013). If confirmed, those genes could potentially be used to predict gout from diuretic use, a first line agent for hypertension and congestive heart failure.
Methods: We examined the potential interaction between urate genes and diuretic use in relation to the risk of incident gout in 6788 women from the Nurses’ Health Study (NHS) and 4012 men from the Health Professionals Follow-up Study (HPFS). Two genetic risk scores (GRS) were created from common urate SNPs for eight previously known genes (GRS8, used by the ARIC study above) as well as for 29 genes (GRS29, a new score incorporating additional novel genes). We ascertained incident gout cases using the American College of Rheumatology survey criteria. We used Cox proportional hazards models for associations and interactions of interest.
Results: Our study included 310 and 674 confirmed cases of incident gout in the NHS and HPFS cohorts, respectively. In the NHS, compared with no thiazide or loop diuretic use, their use was associated with a multivariate RR of 1.97 (95% CI 1.32 to 2.93) among those with a GRS8 below the median and 2.33 (95% CI 1.73 to 3.13) for those with a GRS8 above the median (p for interaction = 0.21) (Table 1). The corresponding RRs according to GRS29 categories were 1.89 (95% CI 1.28 to 2.79) for below the median and 2.39 (95% CI 1.77 to 3.24) for above the median (p for interaction = 0.33). Similarly, two previously purported genes, SLC2A9 (GLUT9) and SLC22A11 (OAT4), showed no significant interactions (p for interactions > 0.05). Corresponding analyses in the HPFS showed no significant interactions (Table 1) (all p values for interaction > 0.28). Further, the lack of interaction persisted in our analyses when limited to those with hypertension in both cohorts, except for SLC22A11 among women, which showed a significant interaction but in the opposite direction to that in the recent ARIC study.
Conclusion: These prospective studies based on a large number of incident cases of confirmed gout indicate that individuals with a genetic predisposition for hyperuricemia are not at an increased risk of developing diuretic-induced gout as compared with those without such a predisposition. These findings do not support the potential utility of these genes to assess gout risk in relation to diuretic use.
|
Table 1. Relative Risk for Incident Gout According to Diuretic Use and Genetic Urate Score Based on 8 Urate SNPs (GRS8) and 29 Urate SNPSs (GRS29) |
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|
|
NHS |
|
HPFS |
|
||||||
|
GRS8 |
Below median |
Above median |
P for interaction |
Below median |
Above median |
P for interaction |
||||
|
Thiazide or loop diuretic use |
No |
Yes |
No |
Yes |
|
No |
Yes |
No |
Yes |
|
|
No. of Cases |
73 |
53 |
120 |
108 |
|
229 |
38 |
404 |
56 |
|
|
Person-Years |
78216 |
13386 |
79389 |
12936 |
|
37835 |
1673 |
37533 |
1836 |
|
|
Age adjusted |
1.00 |
3.89 (2.69, 5.62) |
1.00 |
4.81 (3.67, 6.31) |
0.22 |
1.00 |
4.57 (3.08, 6.76) |
1.00 |
3.10 (2.29, 4.20) |
0.25 |
|
MV adjusted |
1.00 |
1.97 (1.32, 2.93) |
1.00 |
2.33 (1.73, 3.13) |
0.21 |
1.00 |
2.19 (1.41, 3.40) |
1.00 |
1.69 (1.20, 2.37) |
0.28 |
|
GRS29 |
Below median |
Above median |
P for interaction |
Below median |
Above median |
P for interaction |
||||
|
Thiazide or loop diuretic use |
No |
Yes |
No |
Yes |
|
No |
Yes |
No |
Yes |
|
|
No. of Cases |
73 |
57 |
120 |
104 |
|
218 |
35 |
415 |
59 |
|
|
Person-Years |
78292 |
13585 |
79313 |
12737 |
|
37698 |
1705 |
37670 |
1805 |
|
|
Age adjusted |
1.00 |
4.04 (2.82, 5.79) |
1.00 |
4.79 (3.65, 6.30) |
0.38 |
1.00 |
4.19 (2.81, 6.23) |
1.00 |
3.46 (2.56, 4.68) |
0.48 |
|
MV adjusted |
1.00 |
1.89 (1.28, 2.79) |
1.00 |
2.39 (1.77, 3.24) |
0.33 |
1.00 |
2.19 (1.40, 3.42) |
1.00 |
1.88 (1.34, 2.63) |
0.38 |
|
Adjusted for age, BMI, menopause (NHS), use of hormone therapy (NHS), history of hypertension, systolic and diastolic blood pressure, alcohol, total energy intake, and intake of sugar-sweetened soft drinks, meat, seafood, and dairy products. |
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Disclosure:
Y. Bao,
None;
T. R. Merriman,
None;
G. Curhan,
None;
E. A. Stahl,
None;
D. B. Mount,
None;
R. M. Plenge,
None;
P. Kraft,
None;
H. K. Choi,
Takeda Pharmaceuticals International, Inc;,
5,
AstraZeneca,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lack-of-gene-diuretic-interactions-on-risk-of-incident-gout-the-nurses-health-study-and-health-professionals-follow-up-study/