title: Effect of C282Y genotype on self-reported musculoskeletal complications in hereditary hemochromatosis.
abstract: 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]).
  
  
  CONCLUSIONS
  Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.
authors.affiliation: Department of Orthopedics, Centro Hospitalar Lisboa Central, Lisboa, Portugal; Department of Biomedical Sciences and Medicine and Centre of Marine Sciences, University of Algarve, Faro, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Camacho
authors.affiliation: Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Rhumatologie, Paris, France; Institut National de la Santé et de la Recherche Médicale U1132, Hôpital Lariboisière, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Funck-Brentano
authors.affiliation: Department of Biomedical Sciences and Medicine and Centre of Marine Sciences, University of Algarve, Faro, Portugal.
authors.forename: Márcio
authors.initials: M
authors.lastname: Simão
authors.affiliation: Department of Biomedical Sciences and Medicine and Centre of Marine Sciences, University of Algarve, Faro, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Cancela
authors.affiliation: Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Rhumatologie, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ottaviani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1132, Hôpital Lariboisière, Paris, France; Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex 10, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Solal
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1132, Hôpital Lariboisière, Paris, France; Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Fédération de Rhumatologie, Paris Cedex 10, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Richette
mesh_terms: D000368:Aged; D005260:Female; D005293:Ferritins / Q000235:genetics; D005838:Genotype; D006432:Hemochromatosis / Q000150:complications* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000209:etiology* / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics; D057566:Self Report; D014168:Transferrin / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins
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