Effect of C282Y genotype on self-reported musculoskeletal complications in hereditary hemochromatosis

PLoS One. 2015 Mar 30;10(3):e0122817. doi: 10.1371/journal.pone.0122817. eCollection 2015.


Objective: Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype.

Methods: A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status.

Results: In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]).

Conclusion: Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.

MeSH terms

  • Aged
  • Female
  • Ferritins / genetics
  • Genotype
  • Hemochromatosis / complications*
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein
  • Heterozygote
  • Histocompatibility Antigens Class I / genetics
  • Homozygote
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Musculoskeletal Diseases / etiology*
  • Musculoskeletal Diseases / genetics*
  • Osteoarthritis / genetics
  • Osteoporosis / genetics
  • Self Report
  • Transferrin / genetics


  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Transferrin
  • Ferritins

Grant support

The Association Rhumatisme et Travail (Centre Viggo Petersen, Hospital Lariboisière, Paris) funded copyediting (Laura Smales, BioMedEditing) of this report. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.