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Study of iron overload yields surprising results


Early results of the largest and most diverse screening study of a genetic condition that causes too much iron to build up in the body show that Asians and Pacific Islanders have the highest mean levels of iron in their blood of all ethnic groups involved, including African Americans, Caucasians, Hispanics, and Native Americans.

Hemochromatosis, one of the most common inherited disorders among Caucasians, can lead to iron overload, or a buildup of iron in the body’s organs. This extra iron, which can be easily treated if detected early, can increase the risk of diabetes, arthritis, sexual dysfunction, liver disease and liver cancer and heart disease.

When the study is completed, researchers hope to have answers to the key questions that will help policymakers decide whom should be screened for hemochromatosis and iron overload, when should they be screened, and what screening methods should be used.

At the start of the study in 1999, it was known that most cases of hemochromatosis in Caucasians result from a mutation in the hemochromotosis (HFE) gene. The mutation, known as C282Y, was first discovered in 1996. Little was known about iron overload in other racial and ethnic groups.

Surprisingly, results of the Hemochromatosis and Iron Overload Screening Study (HEIRS) show that Asians and Pacific Islanders had the highest blood iron levels but the lowest prevalence of HFE mutations. The full results of the screening study appear in the April 28 issue of the New England Journal of Medicine.

Wake Forest University School of Medicine was the coordinating center for the study, which recruited more than 100,000 participants in primary care settings and seven blood drawing laboratories in the United States and Canada.

The five-year study is funded by the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute. Other major findings of the study include the following:

Caucasians had the highest prevalence of the C282Y mutation in both copies of their HFE gene (4.4 per 1,000 people). Though this is the gene combination most likely the result in hemochromatosis, the risk of developing symptoms is less than 60 percent.
The prevalence rates of this combination in other 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 with the C282Y/C282Y combination had elevated levels of iron in the blood. Men with this genotype were more likely to report a history of liver disease than participants without HFE mutations.

"Our findings help us better understand the prevalence of these conditions in other ethnic groups," said David Reboussin, Ph.D., associate professor of biostatistics at Wake Forest’s School of Medicine. "The result that really surprised us was the finding that Asians and Pacific Islanders had the highest levels of iron in the blood, even though they had the lowest prevalence of the genotype most often associated with hemochromatosis."

Reboussin said it’s possible that Asians and Pacific Islanders may have a different genetic mutation that has not yet been discovered, or perhaps they have high levels of iron, but not hemochromatosis. He said that later phases of the study, which involve a more detailed study visit and follow-up data on these participants from their primary care physicians, will answer these important questions.

The HEIRS study is being conducted at five field centers in the United States and Canada: Howard University (Washington, D.C.), Kaiser Permanente Center for Health Research, Northwest and Hawaii (Portland, Ore., and Honolulu, Hawaii), London Health Sciences Centre (London and Toronto, Ontario), University of Alabama at Birmingham, and University of California, Irvine.

Karen Richardson | EurekAlert!
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