To date, concentrations of the promising biomarker hepcidin have only been assessed in serum of relatively small series of healthy volunteers and patients. We assessed age-and sex-stratified reference ranges of serum hepcidin concentration in a selected reference set and performed regression analyses to study associations between hepcidin and (biochemical) variables in a large, wellphenotyped sample of the general population (n ؍ 2998). All participants filled out a questionnaire on lifestyle, health status, and medical history. Serum measurements of iron parameters, liver enzyme alanine aminotransferase, creatinine and C-reactive protein were available. Serum hepcidin concentrations were lower for premenopausal than for postmenopausal women (median, 4.1nM vs 8.5nM, respectively). Hepcidin concentrations in men were constant over age (median, 7.8nM).
Objective. To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF ؊173G>C and CATT 5-8 alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA).Methods. Genotyping was performed in patients with early RA and in healthy controls. Demographic data, disease activity, and outcome measurements were compared between patients with and without the MIF variants. MIF ؊173G>C and CATT 5-8 polymorphisms were genotyped, and a newly developed enzyme-linked immunosorbent assay for human MIF was used. Allele and genotype distributions of the MIF ؊173G>C and CATT 5-8 polymorphisms were compared between patients and controls by chi-square test. Multiple regression analysis was performed to assess the independence of the MIF functional genetic variants as risk factors for radiologic joint damage.Results. Genotyping of the ؊173G>C and CATT 5-8 polymorphisms of MIF in RA patients and healthy individuals (n ؍ 277 each) revealed similar frequencies of genotypes and haplotypes in both groups. No significant differences in demographic or clinical features were observed between RA patients carrying the MIF ؊173C allele or the MIF CATT 7 allele or both and noncarrier RA patients. Radiologic joint damage was significantly higher in patients carrying risk alleles of the MIF ؊173G>C or the MIF CATT 5-8 functional variants. No synergistic effects between both genetic variants were observed. Multivariate regression analysis revealed that presence of the MIF ؊173C/C and MIF CATT 7/7 genotypes and having 1 MIF ؊173C allele were independent prognostic variables. Carriership of the MIF ؊173C allele (P ؍ 0.002) or MIF CATT 7 allele (P ؍ 0.004) was associated with significantly higher circulating MIF levels compared with those in subjects having none of the risk-conferring alleles, and greater circulating MIF levels correlated with more severe radiologic joint damage (r ؍ 0.64, P ؍ 0.001).Conclusion. The MIF polymorphisms are not associated with RA susceptibility but are associated with high levels of radiologic joint damage. High circulating MIF levels were shown to correlate strongly with radiologic joint damage, suggesting that MIF expression is genetically determined and can be used as a novel prognostic tool in RA.
BACKGROUND:Hepcidin is an iron-regulatory peptide hormone that consists of 3 isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are sparse, as is knowledge of their relative analytical strengths and clinical utility.
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