Scientists shed new light on common genetic disorder
A genetic defect in the liver is behind an iron overload disorder which affects one in 300 people, German researchers have discovered. The work, which was partly funded by the EU, is published in the journal Cell Metabolism. Iron plays an important role in a number of metabolic processes, and it is a vital component of red blood cells. However, while a lack of iron can lead to problems such as anaemia, too much iron can be equally dangerous as it promotes the formation of toxic radicals that cause tissue damage. For this reason, our bodies have mechanisms in place to ensure that iron levels are high enough to meet our body's needs, but not high enough to inflict damage on our organs and tissues. This involves reacting to signals from systems that absorb iron and sending signals to cells that supply iron, such as cells in our intestines that take up iron from our diet. Hereditary hemochromatosis is a genetic iron overload disorder which affects around one in 300 people, making it probably the most common genetic disorder in Europe. Sufferers absorb and store too much iron from their diet. Excess iron is stored around the body in organs including the pancreas, liver and skin. Symptoms include joint pain, fatigue, lack of energy, abdominal pain and heart problems as well as bronzed skin. It is treated by the regular removal of blood; this prompts the body to draw on the excess stored iron to replace the red blood cells lost. If left untreated, it can lead to diseases such as liver cancer, heart failure, arthritis and thyroid deficiency. In 1996, scientists discovered that the disease is caused by mutations in a gene called HFE. However, until now, the organ where HFE is active has remained a mystery. In this latest study, the scientists created mice in which the HFE gene had been switched off in different tissues. They found that mice whose livers lacked HFE showed all the classic features of the disease. 'For a long time scientists thought of HH as a disease of the intestine, because this is where iron uptake actually takes place,' commented Matthias Hentze of the European Molecular Biology Laboratory (EMBL). 'Our research now reveals the crucial point is actually the liver and explains why HH patients suffer from increased iron absorption.' The HFE gene codes for a protein which is responsible for transmitting information on the body's iron levels to the liver cells. If iron levels are too high, the liver cells produce a hormone called hepcidin, which causes the intestines to reduce their iron uptake. 'HFE influences hepcidin expression through a series of intermediate molecules, but when the HFE gene is mutated the result is that less hepcidin is produced,' explained Martina Muckenthaler of the University of Heidelberg. 'This in turn means iron uptake in the intestine cannot be limited as effectively and an overload develops.' EU support for the work came from the Euroiron1 project, which is funded under the 'Life sciences, genomics and biotechnology for health' priority of the Sixth Framework Programme (FP6). Earlier this year, scientists from the project demonstrated that two proteins responsible for iron regulation are also vital for regulating the uptake of water and nutrients from our intestine.
Countries
Germany