title: Phenotypic expression in detected C282Y homozygous women depends on body mass index.
abstract: OBJECTIVE
  In HFE-related haemochromatosis, a large proportion of C282Y homozygotes, especially women, are not detected by phenotypic screening using transferrin saturation. The aim of this study was to identify the clinical and biochemical factors associated with non-expression of the disease as defined as transferrin saturation <45%.
  
  
  METHODS
  The study was performed in 78 (57 women and 21 men) C282Y homozygotes identified through a large-scale screening program conducted on 19,644 French subjects. Biometric, clinical and biochemical variables including those susceptible to influence body iron stores were tested for association with transferrin saturation levels <45%.
  
  
  RESULTS
  Non-expression was observed in 26/57 (46%) women and in 5/21 (24%) men. At multivariate analysis, female gender (OR: 16.5, 95%CI 1.8-146.5; P = 0.012), body mass index (OR: 1.21, 95%CI 1.02-1.44; P = 0.027), haemoglobin levels (OR: 0.88, 95%CI 0.81-0.97; P = 0.012) and serum ferritin levels (OR: 0.99, 95%CI 0.98-1.00; P = 0.007) were significantly and independently associated with a non-expressing phenotype.
  
  
  CONCLUSIONS
  Excess body mass is commonly associated with the lack of phenotypic expression in detected C282Y homozygotes. This should be kept in mind with respect to the design and cost-effectiveness of phenotypic screening programs for haemochromatosis.
authors.affiliation: Centre d'Investigation Clinique INSERM 0203, CHU Pontchaillou, 35033 Rennes, France. fabrice.laine@chu-rennes.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lainé
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Jouannolle
authors.forename: Jeff
authors.initials: J
authors.lastname: Morcet
authors.forename: Alain
authors.initials: A
authors.lastname: Brigand
authors.forename: Michel
authors.initials: M
authors.lastname: Pouchard
authors.forename: Bernard
authors.initials: B
authors.lastname: Lafraise
authors.forename: Jean
authors.initials: J
authors.lastname: Mosser
authors.forename: Véronique
authors.initials: V
authors.lastname: David
authors.forename: Yves
authors.initials: Y
authors.lastname: Deugnier
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012737:Sex Factors; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin