Background – Approximately 12% of people of Northern European descent are heterozygous for the C282Y mutation of the HFE gene (homozygosity for which mutation is associated with hereditary haemochromatosis). Improved phenotypic characterization is needed to assess health risks for the heterozygote genotype.
Objective – To determine the relative importance of HFE genotype, diet, lifestyle, and blood loss for predicting iron status in a sample of UK men aged 40 years or over.
Design – Iron status (serum ferritin (SF), transferrin saturation (TS), soluble transferrin receptor (sTfR)) was measured in 44 C282Y heterozygote and 85 age- and BMI-matched wildtype men. Dietary intake of iron (total, haem and non-haem), and components that influence iron bioavailability, was determined using a validated Meal- Based Intake Assessment Tool. Lifestyle and blood loss data were obtained by questionnaire, and height and weight measured. Linear mixed models were used to determine the predictors of iron status controlling for matching. Outcomes – C282Y heterozygosity was associated with 18% higher TS (95% CI: 7%, 31%) but no difference in SF or sTfR concentrations. Blood donation was negatively associated with TS (-13% (-3%, -22%)) and SF (-58% (- 44%, -68%)), and had a marginally significant positive association with sTfR concentration. Self-reported faecal blood loss was negatively associated with SF concentration (-35% (-54%, -7%)). Alcohol was the only dietary variable associated with iron status and was associated with all three of the iron status indices. Serum ferritin concentration was positively associated with BMI (10% increase per BMI unit increase (6%, 15%)).
Conclusions – Blood loss was a stronger predictor of iron status than either C282Y heterozygosity or diet in this population of UK men.