title: Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study.
abstract: BACKGROUND
  Age, gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA). Iron increases are associated with age and gene mutation. In the present study, we examined whether serum ferritin, an indicator of total body iron stores, correlates with clinical features in patients with OA, and whether the hemochromatosis Fe (HFE) gene mutation plays a role.
  
  
  METHODS
  In a 2-year longitudinal observational study, 127 patients with knee OA and 20 healthy individuals (controls) were enrolled. All patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs. Peripheral blood samples were analyzed for serum ferritin, and genotyped for HFE using allelic discrimination methods.
  
  
  RESULTS
  Higher levels of serum ferritin were found in patients older than 56 years (P =0.0186) and males (P =0.0006), with a trend toward higher ferritin in patients with OA. HFE gene mutation carriers were more prevalent among patients with OA than among healthy controls. When stratified further by gender, we found that male patients with OA had higher levels of serum ferritin than male control subjects [odds ratio = 4.18 (limits of 95% confidence interval: 0.86-27.69, P = 0.048)]. Analyses of radiographic data indicated that higher ferritin was associated with narrower joint space width at baseline (P = 0.032) in male patients. Additionally, among men, risk prediction of radiographic severity [Kellgren-Lawrence (KL) grade >2)] in the higher ferritin group was almost five times that of the lower ferritin group (odds ratio = 4.74, P = 0.023).
  
  
  CONCLUSIONS
  Our data suggest that increased ferritin levels are associated with symptomatic knee OA in males. This finding needs to be validated in a larger cohort of patients.
authors.forename: Lauren
authors.initials: L
authors.lastname: Kennish
authors.forename: Mukundan
authors.initials: M
authors.lastname: Attur
authors.forename: Cheongeun
authors.initials: C
authors.lastname: Oh
authors.forename: Svetlana
authors.initials: S
authors.lastname: Krasnokutsky
authors.forename: Jonathan
authors.initials: J
authors.lastname: Samuels
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Greenberg
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Division of Rheumatology, Department of Medicine, New York University School of Medicine, NYU Hospital for Joint Diseases, New York, NY, USA. stevenb.abramson@nyumc.org.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Abramson
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005293:Ferritins / Q000097:blood*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D020370:Osteoarthritis, Knee / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D010641:Phenotype; D011446:Prospective Studies; D011859:Radiography; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins