By Nicole MacKee
UK researchers have found that a common genetic variant associated with haemochromatosis substantially increases the risk of a range of diseases, prompting calls for population screening to enable early detection and intervention.
In a study published in the BMJ, researchers analysed the data of almost 3000 UK community dwellers of European descent (aged 40 to 70 years) who were homozygous for the genetic variant HFE p.C282Y.
When compared with people without the mutation, men who were homozygous were found to be at increased risk of diagnosed haemochromatosis, any liver disease, diabetes mellitus and rheumatoid arthritis or osteoarthritis, whereas homozygous women were found to be at increased risk of haemochromatosis and osteoarthritis.
Professor Darrell Crawford, Professor of Hepatology at The University of Queensland, said the complications of haemochromatosis were, in general, related to the extent of iron loading, which was usually greater in men because of the protective effect of menses in women.
He said the overall penetrance found in the study – 38.3% in homozygous men and 27.2% in homozygous women – was higher than expected. The study authors pointed to one previous study in which the penetrance for haemochromatosis was estimated to be less than 1%.
‘These results provide a new perspective on the value of population screening and should cause a reconsideration of its value. Early diagnosis and intervention before excess iron accumulates is the cornerstone of population screening for haemochromatosis,’ Professor Crawford said.
‘Population screening may have greater importance now that the obesity epidemic is upon us, since fatty liver disease in patients with haemochromatosis promotes further liver injury and there is some evidence that excess iron alters insulin sensitivity to further increase the risk of diabetes mellitus.’
Professor Crawford said it was concerning to see that, despite the participants’ mean age of almost 57 years, only 12.1% of men and 3.4% of women had a baseline diagnosis of haemochromatosis.
‘This did increase during the study, but the low rate of diagnosis is concerning and indicates the need for increased educational campaigns for both clinicians and the community about this disease,’ he said.
Although venesection is an effective therapy for many people with iron overload, Professor Crawford’s research team is participating in a global study investigating hepcidin therapy as an alternative therapy for the substantial number of patients who have difficult venous access.
BMJ 2019; 364: K5222.