Phenotypic expression in detected C282Y homozygous women depends on body mass index

Background/Aims 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.