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Iron Overload Strikes All Races

Disease thought to affect mostly whites also found in Asians, Pacific Islanders

WEDNESDAY, April 27, 2005 (HealthDay News) -- New research contradicts the belief that the iron-overload disease hemochromatosis strikes mostly white people of Northern European descent.

The study, published in the April 28 issue of the New England Journal of Medicine, found that high iron levels can be found across all races, and that Asians and Pacific Islanders living in North America had higher iron levels than people from other races.

However, the study also found that Asians and Pacific Islanders had the lowest prevalence of the known genetic mutations that cause hemochromatosis.

The finding suggests there are other genetic mutations yet to be discovered that play a part in iron overload, experts said.

Across the board, according to the study, almost 9 percent of the 100,000 people from all races who were tested had elevated levels of stored iron.

"I think many people will be startled by how common this is," said study co-author Dr. Paul Adams, a professor of medicine at the London Health Sciences Center in London, Ontario. "The typical genetic pattern for hemochromatosis was present in one in 227 Caucasians, making this one of the most common genetic diseases. It's 10 times as common as cystic fibrosis."

High iron levels can contribute to the development of diabetes, fatigue, sexual dysfunction, liver disease and severe arthritis, Adams said.

But since these conditions don't develop overnight, if you are diagnosed with high iron levels, you can be treated.

Adams and his colleagues recruited 99,711 adults over the age of 25 from five different centers in the United States and Canada. Forty-four thousand of the study participants were white, 27,124 were black, 12,772 were Asian, 12,459 were Hispanic, 1,928 were of multiple or unknown race, 698 were Pacific Islander, and 648 were Native American.

There are two known genetic mutations to the HFE gene that are involved in hemochromatosis: C282Y and H63D. To get hemochromatosis, you must inherit a mutated copy of the HFE gene from each parent, although not everyone who has genetic mutations from both parents develops hemochromatosis.

In this study, 299 people had two C282Y mutations. Slightly more than 1,000 had C282Y from one parent and H63D from the other, and 1,270 had two copies of the H63D mutation.

The mutations were found far more commonly in whites than in people of other races. For example, 0.44 percent of whites had two C282Y mutations, while this pattern was found only in 0.11 percent of Native Americans, 0.027 percent of Hispanics, 0.014 percent of blacks, 0.012 percent of Pacific Islanders and in 0.000039 percent of Asians.

However, far more people had signs of elevated iron levels than had the known genetic mutations. More than 8,600 people in the study had elevated levels of ferritin (over 400 micrograms per liter). Ferritin levels are a marker of the amount of iron stored in the body. High levels can indicate iron overload.

Pacific Islanders were the group most likely to have high ferritin levels, with more than 25 percent with levels over 400 micrograms per liter. Nineteen percent of Asians had elevated ferritin levels, while 9.7 percent of blacks did. More than 6 percent of Native Americans had high ferritin levels, compared to 5.3 percent of Hispanics and just 5.9 percent of whites.

High ferritin levels don't always mean iron overload, however. Adams noted that other conditions, such as inflammation, liver disease and high alcohol consumption, can increase ferritin levels.

"Based on the Adams study and other large studies, it's apparent that not everyone who has the most frequent mutations will have expression of disease," said Dr. Bruce Bacon, who co-authored an accompanying perspective article. "And, there are Asians and South Pacific Islanders who have abnormal iron studies, yet don't have the genetic mutations."

That suggests, he said, that there are probably other unknown genes or mutations responsible for iron overload in other races.

"Iron homeostasis is a very complicated process, and we are just getting our arms around a little bit of the process to understand how iron absorption is regulated," said Bacon, who is director of the division of gastroenterology and hepatology at Saint Louis University, in St. Louis.

Adams said the study will continue and they'll probably search for other genes involved in iron overload, as well as looking in more detail at the health effects of high iron levels and considering the feasibility of hemochromatosis screening tests.

More information

If you'd like to learn more about hemochromatosis, visit the National Library of Medicine.

SOURCES: Paul Adams, M.D., professor, medicine, London Health Sciences Center, London, Ontario; Bruce Bacon, M.D., director, division of gastroenterology and hepatology, and professor, internal medicine, Saint Louis University, St. Louis; April 28, 2005, New England Journal of Medicine
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