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Surprising findings reported about iron overload

UAB and international scientists studying iron-overload disorders have made the unexpected discovery that Asians and Pacific Islanders have the highest levels of iron in their blood of all racial/ethnic groups who were screened.

Individuals who develop hemochromatosis/iron overload absorb an excessive amount of iron from food and supplements ingested. The abnormality affects many people worldwide, is prevalent in the South, and sometimes causes organ damage when severe iron deposition occurs due to inadequate control of iron absorption by the small intestine.

The first major report of findings in the five-year, 100,000-person study will be published tomorrow, April 28, in The New England Journal of Medicine (NEJM). The University of Alabama at Birmingham received $3.1 million of study funds to screen 20,000 people for the group of disorders called hemochromatosis and iron overload.

Ronald T. Acton, Ph.D., professor of microbiology and director of the UAB Immunogenetics Program, is principal investigator for the Birmingham Field Center that did the screening. James C. Barton, M.D., director of the Southern Iron Disorders Center and UAB clinical professor of medicine, is co-principal investigator. They exceeded the goal of screening 10,000 African-Americans and 10,000 whites for blood iron levels or the presence of mutations in a gene, called the HFE gene, which evidence suggests regulates iron absorption.

"Hemochromatosis and iron overload are easily treatable if diagnosed early, but the simple blood test that could detect these conditions is not performed as part of routine medical exams," said Acton. Delaying treatment ?the weekly removal of a pint of blood by phlebotomy ?can permit the progressive accumulation of iron deposits in target organs that may result in complications such as cirrhosis of the liver, liver cancer, arthritis, diabetes, impotence and heart failure.

"The finding that Asians and Pacific Islanders have high levels of iron in the blood is surprising because they also have the lowest prevalence of the particular gene mutation that is found in Caucasians with the typical form of hemochromatosis," he said. "This may mean that the Asians and Pacific Islanders have a different genetic mutation that has not yet been discovered, or that they do not, for some reason, develop hemochromatosis/iron overload despite their high blood levels of iron."

He said that the NEJM paper is the first report from analysis of the massive data arising from the study, called the Hemochromatosis and Iron Overload Screening (HEIRS) Study. The study is funded by the National Heart, Lung and Blood Institute and the National Human Genome Research Institute.

The other HEIRS Study Field Centers were located at University of California, Irvine; London Health Sciences Centre, Ontario, Canada; Howard University, Washington, D.C.; and Kaiser Permanente Center for Health Research (Oregon and Hawaii). Wake Forest University in Winston-Salem, N.C. coordinated the Study, and the Study's Central Laboratory is located at the University of Minnesota in Minneapolis.

At the beginning of the study in 2000, it was known that most cases of hemochromatosis in Caucasians resulted from common mutations in the HFE gene, first discovered in 1996. At that time, little was known about the causes of iron overload in other racial/ethnic groups.

Major findings of the study include:

* Caucasians had the highest prevalence of persons who had two copies of the C282Y mutation of the HFE gene (4.4 per 1,000 people).
* Prevalence of two copies of the C282Y mutation of the HFE gene in other racial/ethnic groups were: Native Americans (1.1 per 1,000), Hispanics (2.7 per 10,000), African-Americans (1.4 per 10,000), Pacific Islanders (1.2 per 10,000) and Asians (3.9 per 10 million).
* Most participants who had two copies of the C282Y mutation of the HFE gene also had elevate d levels of iron in their blood.
* Men who had two copies of the C282Y mutation of the HFE gene were more likely to report a history of liver disease than participants without HFE mutations.

"Our findings in Caucasians confirm reports from previous smaller studies," said Acton. "Our findings in non-Caucasians help everyone understand the prevalence of these conditions in other racial/ethnic groups."

He added that many white Alabamians have Celtic origins, with some counties reporting Irish ancestry in 17 percent of the population. "The hemochromatosis C282Y mutation is thought to have occurred among Celtic or Scandinavian populations 1,500-3,000 years ago, and the mutation may have helped them survive iron-poor diets."

Hemochromatosis or iron overload occur in 0.3-0.5 percent of white persons of northern, central, and western European descent. In fact, a health-screening program conducted by Barton and Acton at an Alabama forest products mill detected the disorder in 0.39 percent of all white participants, and 0.53 percent of white men.

Acton and Barton said they hope that results of the study will prompt more primary care physicians to consider hemochromatosis and iron overload as a diagnosis. Nationwide studies indicate it takes an average of nine years and three physicians to obtain a correct diagnosis, partly because physicians incorrectly believe that such disorders are rare, or that they affect only older men. A previous UAB study found that primary care physicians provided fewer than 70 percent correct responses about screening at-risk populations for hemochromatosis, iron overload, and associated abnormalities.

As the HEIRS Study shows, iron overload was mistakenly believed to be a disorder that is limited to Caucasians, said Acton. He, Barton, and others have begun studying the role of iron overload and HFE mutations in the development of type 2 diabetes in persons of various racial/ethnic groups.


Source:University of Alabama at Birmingham

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