Irvine, Calif., Nov. 12, 2014 — Researchers at the UC Irvine School of Medicine have received a $2.04 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases to study genetic modifiers of iron status in hemochromatosis, a hereditary disease in which affected persons suffer excessive dietary iron absorption.
Christine McLaren, professor of epidemiology, and Dr. Gordon McLaren, professor of hematology and oncology and a staff physician at the Veterans Affairs Long Beach Healthcare System, will lead a multi-disciplinary team of investigators at eight research institutions in the U.S., Canada and Australia.
“Approximately one million people in the U.S. are at risk for development of iron overload, attributable primarily to the genetic disorder known as hemochromatosis,” said Christine McLaren, a co-principal investigator. “Once considered a rare disease, hemochromatosis is now recognized as one of the most common inherited disorders, occurring in approximately five persons per 1,000 in populations of northern European descent.”
Some patients accumulate toxic levels of iron, causing damage to multiple organs and complications such as liver cirrhosis, hepatocellular carcinoma, heart failure, diabetes, arthritis and impotence. Others have less severe iron overload and do not experience such disease manifestations.
To better understand the reasons for this variability in disease expression, the investigators will examine genetic factors in the susceptibility or resistance to iron overload in patients with hemochromatosis across a wide range of geographic areas.
Most patients with hereditary hemochromatosis carry two copies of a specific variant of the hemochromatosis gene. Persons affected suffer from an inability to limit absorption of dietary iron, leading to increased body iron stores. Some, but not all, patients with this variant develop severe iron overload.
It is important to identify persons at risk, because effective iron-removal treatment is available, and beginning such therapy before iron overload becomes advanced can prevent disease complications. The reasons for the variability in severity among persons who carry the gene is not known. The purpose of this research is to identify other inherited traits that may interact to cause more severe disease in certain patients.
The project will be conducted at the UC Irvine School of Medicine in the Department of Epidemiology and the Division of Hematology/Oncology, and at the Veterans Affairs Medical Center in Long Beach, Calif. Samples will be processed by the UC Irvine Institute for Clinical & Translational Science Functional Genomic Core.
The UC Irvine Chao Family Comprehensive Cancer Center will assist with data collection and analysis. This NIH award will establish a U.S. consortium with international partners to collect information from a broad collection of hemochromatosis patients and subjects enrolled in screening studies and clinical practice.
The three-year, multi-center project will provide insight into possible genetic contributions to susceptibility or resistance to iron overload. Results will help to understand the significant variation in iron loading in different individuals with this disorder and the relationship to clinical manifestations.
This could have important clinical applications, including the ability to identify young hemochromatosis patients at risk for potentially severe iron overload later in life, thereby informing recommendations regarding initiation of iron-removal therapy and long-term follow-up of iron stores and related manifestations. This approach may ultimately lead to development of innovative prevention and treatment strategies tailored to the individual.
“This award highlights the exceptional level of expertise and important contributions of the Department of Epidemiology and Division of Hematology/Oncology in genetic epidemiology and particularly in studying genetic contributions to iron metabolism,” said Dr. Gordon McLaren, co-principal investigator. “The award will position UC Irvine as a center for genomic studies of hemochromatosis. We will use state-of-the-art genetic techniques to examine iron-related genetic regions to identify causal variants associated with severe or mild iron expression in hemochromatosis patients.”
The grant also permits UC Irvine to provide collaborative awards to Dr. Paul C. Adams at the London Health Sciences Centre in Ontario, Canada; Dr. James C. Barton, director of the Southern Iron Disorders Center in Birmingham, Ala.; Dr. Pradyumna D. Phatak, medical director, Cancer Center, Rochester General Hospital, Rochester, NY; John D. Phillips, research associate professor in the Division of Hematology and Hematologic Malignancies at the University of Utah; Mary J. Emond, research associate professor at the University of Washington; Lyle C. Gurrin, associate professor at the University of Melbourne, Australia; and Nathan Subraminiam, professor at the Queensland Institute of Medical Research/Berghofer Medical Research Institute in Brisbane, Australia.
This research is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (grant 1 R24DK099846 01A1).