Tahzeeb F.1, Merriman T.1, Iverson C.2, Miner J.2
Affiliation(s):
1University of Otago, Dunedin, New Zealand. 2Ardea Biosciences, Inc., San Diego, CA, USA
Background: Iron homeostasis is a tightly regulated set of biochemical processes. Transferrin and its cell-surface receptor regulate iron uptake and ferritin sequesters free iron and acts as a store for excess iron from intra- and extra-cellular pools. Ferritin has been positively associated with serum urate in the National Health and Nutrition Examination Survey III (NHANES III) [1]. There have been observational and interventional studies suggesting a role for iron as a trigger for gout flares, which may be due to a number of pro-inflammatory activities associated with iron [2, 3]. Consistent with this, genetic variation in the transferrin receptor is associated with gout and with an increased likelihood of self-report of an iron-rich food as a trigger of flares.
Objective: To replicate the association of ferritin with serum urate and to test for association of ferritin with gout.
Methodology: For the serum urate association analysis, African-American subjects from the publicly available Jackson Heart Study were included (693 females and 567 males). Subjects who self-reported taking diuretic or urate-lowering medication/s, or who had kidney disease or gout, were excluded. For the gout analysis 93 individuals were included, comprising 60 controls (all males) and 33 gout cases (4 females and 29 males). Linear regression analysis using R 3.2.0 and adjusting for age and body mass index was done to test for association between ferritin and serum urate. An unpaired t test was used to test for association between gout and plasma ferritin.
Findings: A positive association of serum ferritin and urate was found in both males (ß=1.02E-04 pmol/L, P=9.6E-03) and females (ß=1.95E-04pmol/L, P=7.1E-04) in the Jackson Heart Study. Plasma concentrations of ferritin were elevated in gout cases (Mean±SD; 320.6±167.1 ng/mL) compared to controls (69.45±63.41 ng/mL) (P<1x10–4).
Conclusion and significance: The associations between ferritin and both serum urate and gout implicate iron metabolism in gout. While it is not possible to assign causality from this observational study, the previously reported association of the transferrin receptor with gout [1] is consistent with iron metabolism having a causal role in gout.
References: 1. Ghio AJ, et al. Free Radic Res. 2005;39(3):337-42. 2. Facchini FS. Rheumatology. 2003;42:1550-5. 3. Dabbagh AJ, et al. Ann Rheum Dis. 1992;51:516–21.