Asians, Pacific Islanders Have Highest Blood Iron Levels

BIRMINGHAM, Ala. -- 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 elevated 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.