The relationship between ferritin and urate levels and risk of gout

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.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1668-y) contains supplementary material, which is available to authorized users.

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“…So, the association between ferritin level and serum uric acid was independent of CRP, suggesting that the relationship is not due to an elevation of ferritin in inflammation and consistent with the direct role of iron metabolism in the control of serum uric acid and gout. This is supported by the previous report of an association of transferrin receptor in gout 11 . This is the first study conducted to explore the relationship between serum uric acid level and iron markers in relation to gout in Saudi patients.…”

“…In Saudi Arabia, people rely more on the nonvegetarian diet compared to vegetarian food, so there is always an increased possibility of recurrence of gout flairs. Based on these observations, the present study was conducted to evaluate the association between serum ferritin, uric acid, and iron overload in Saudi patients 11 .…”

“…The iron is stored in ferritin as a compact, safe way to prevent the toxic effects of iron and make iron available when necessary; therefore, serum ferritin is widely used to evaluate iron level and status in clinical practice 21 . The relationship of serum ferritin, the hemoglobin with hyperuricemia, could be a response to oxidative stress linked with the visceral toxicity of excess non-transferrin bound iron via the antioxidant properties of serum uric acid 11 .…”

Association between anemia and hyperuricemia: results from the Korean National Health and Nutrition Examination Survey

“…Subsequently, iron deficiency anemia may be the most common type in non-CKD subjects, which accounts for most of the population of this study. In previous studies, positive correlations between ferritin, iron, and serum urate levels have been demonstrated 49,50 . Therefore, hyperuricemia is less likely to occur with anemia in non-CKD subjects, in whom iron deficiency anemia is a major component.…”

The Paradoxical Role of Uric Acid in Osteoporosis

“…Plasma UA levels are higher than plasma ascorbic acid levels, and UA has a higher reduction potential that leads to less iron and copper production, which is important for the Fenton reaction and hydroxyl radical generation [32,33]. Additionally, UA is an iron chelator to reduce iron-catalyzed oxidative stress reaction [34,35,36]. UA at physiologic concentrations has the ability to scavenge reactive oxygen species (ROS) and protect the erythrocyte membrane from lipid oxidation and further hemolysis [37].…”