Abstract
BackgroundFerritin 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.MethodsEuropean (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.ResultsSerum 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 (β (mg dl− 1) = 0.014, p = 2.5E–04), JHS (β = 0.009, p = 3.2E–05) and NHANES III (European β = 0.007, p = 5.1E–11; African American β = 0.011, p = 2.1E–16) data sets but not in NZ European (β = 0.009, p = 0.31) or US (β = 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.ConclusionsThese 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.
Highlights
Ferritin positively associates with serum urate and an interventional study suggests that iron has a role in triggering gout flares
Biochemical observational association analysis Association with serum urate concentration Serum ferritin concentration was positively associated with serum urate concentration in nongout African American individuals from the Jackson Heart Study (JHS) (males β per 10 ng ml− 1 increase = 0.007, p = 9.3E–03; females β = 0.014, p = 1.7E– 03) and National Health and Nutrition Examination Survey (NHANES) III as well as Europeans from the NHANES III study (Table 1)
We extended the previously reported associations of serum ferritin with serum urate [3, 4] using adjustment by C-reactive protein (CRP) to exclude the possibility that the relationship is a consequence of the association of ferritin with inflammatory states, since there is evidence that serum urate levels drop in acute inflammation in hospitalized patients [32]
Summary
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. Ferritin has been positively associated with serum urate in both the US National Health and Nutrition Examination Survey (NHANES) [3] and the China Health and Nutrition Survey [4] with elevation in serum urate suggested as an indicator of iron overload [5]. Iron could contribute to gouty inflammation by forming complexes with MSU crystals, stimulating oxidative stress through the generation of reactive oxygen species, and contributing to granulocyte and complement activation [6]. A decrease in gout flares following phlebotomy to attain near iron-deficient levels in hyperuricemic patients [7] is suggestive of a role in gout
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
