Abstract
Background: Ferritin positively associates with serum urate and an interventional study suggests that iron has a role in triggering gout flares. The objective of this study was to further explore the relationship between iron/ferritin and urate/gout.
Methods: European (100 cases, 60 controls) and Polynesian (100 cases, 60 controls) New Zealand (NZ) males and 189 US male cases and 60 male controls participated. The 10,727 participants without gout were from the Jackson Heart (JHS; African American = 1260) and NHANES III (European = 5112; African American = 4355) studies. Regression analyses were adjusted for age, sex, body mass index and C-reactive protein. To test for a causal relationship between ferritin and urate, bidirectional two-sample Mendelian randomization analysis was performed.
Results: Serum ferritin positively associated with gout in NZ Polynesian (OR (per 10 ng ml(-1) increase) = 1.03, p = 1.8E-03) and US (OR =1.11, p = 7.4E-06) data sets but not in NZ European (OR= 1.00, p = 0.84) data sets. Ferritin positively associated with urate in NZ Polynesian (beta (mg dl(-1)) = 0.014, p = 2.5E-04), JHS (beta = 0.009, p = 3.2E-05) and NHANES III (European beta = 0.007, p = 5.1E-11; African American beta = 0.011, p = 2.1E-16) data sets but not in NZ European (beta = 0.009, p = 0.31) or US (beta = 0.041, p = 0.15) gout data sets. Ferritin positively associated with the frequency of gout flares in two of the gout data sets. By Mendelian randomization analysis a one standard deviation unit increase in iron and ferritin was, respectively, associated with 0.11 (p = 8E-04) and 0.19 mg dl(-1) (p = 2E-04) increases in serum urate. There was no evidence for a causal effect of urate on iron/ferritin.
Conclusions: These data replicate the association of ferritin with serum urate. Increased ferritin levels associated with gout and flare frequency. There was evidence of a causal effect of iron and ferritin on urate.