Our laboratory has had a long-term interest in the clinical aspects and population prevalence of the common iron overload disease haemochromatosis and we have accumulated a very large database of haemochromatosis families. Studies in this area are being carried out under the guidance of Professor Lawrie Powell.
Haemochromatosis results from mutations in the HFE gene and, in Australia, almost all disease is due to a single mutation (C282Y). Current projects include (1) an investigation of the rate of iron accumulation in haemochromatosis patients, particularly those who are apparently not expressing the disease when initially genotyped; (2) analysis of the clinical expression of the disease in C282Y/H63D compound heterozygotes; (3) the identification of genetic modifiers of the iron loading phenotype in haemochromatosis; (4) evaluating the effects of environmental factors on disease phenotype; and (5) investigating the molecular basis of iron overload in patients without HFE mutations.
These studies are being carried out in collaboration with Associate Professor Katie Allen at the Murdoch Institute, Melbourne, Dr Lyle Gurrin and members of the HealthIron Study at the University of Melbourne, Professor John Olynyk at the University of Western Australia and Drs Grant Ramm and Nathan Subramaniam at QIMR. In addition to our haemochromatosis studies, we have initiated investigations into the role played by iron in the pathogenesis of other liver diseases. Of particular interest are alcoholic liver disease and fatty liver disease, both major public health problems in Australia. In the former, hepatic hepcidin levels decline, whereas in the latter, they increase. We are currently investigating the molecular mechanisms that lead to altered hepcidin expression in these conditions. These studies are being carried out in collaboration with Professor Darrell Crawford at Greenslopes Hospital and Drs Linda Fletcher, Kim Bridle and Graeme MacDonald at the Princess Alexandra Hospital in Brisbane.