Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

doi:10.1056/NEJMoa041534

Volume 352:1769-1778		April 28, 2005		Number 17

Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

Paul C. Adams, M.D., David M. Reboussin, Ph.D., James C. Barton, M.D., Christine E. McLaren, Ph.D., John H. Eckfeldt, M.D., Ph.D., Gordon D. McLaren, M.D., Fitzroy W. Dawkins, M.D., Ronald T. Acton, Ph.D., Emily L. Harris, Ph.D., M.P.H., Victor R. Gordeuk, M.D., Catherine Leiendecker-Foster, M.S., Mark Speechley, Ph.D., Beverly M. Snively, Ph.D., Joan L. Holup, M.A., Elizabeth Thomson, M.S., R.N., Phyliss Sholinsky, M.S.P.H., for the Hemochromatosis and Iron Overload Screening (HEIRS) Study Research Investigators

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ABSTRACT

Background Iron overload and hemochromatosis are common, treatableconditions. HFE genotypes, levels of serum ferritin, transferrinsaturation values, and self-reported medical history were studiedin a multiethnic primary care population.

Methods Participants were recruited from primary care practicesand blood-drawing laboratories. Blood samples were tested fortransferrin saturation, serum ferritin, and C282Y and H63D mutationsof the HFE gene. Before genetic screening, participants wereasked whether they had a history of medical conditions relatedto iron overload.

Results Of the 99,711 participants, 299 were homozygous forthe C282Y mutation. The estimated prevalence of C282Y homozygoteswas higher in non-Hispanic whites (0.44 percent) than in NativeAmericans (0.11 percent), Hispanics (0.027 percent), blacks(0.014 percent), Pacific Islanders (0.012 percent), or Asians(0.000039 percent). Among participants who were homozygous forthe C282Y mutation but in whom iron overload had not been diagnosed(227 participants), serum ferritin levels were greater than300 µg per liter in 78 of 89 men (88 percent) and greaterthan 200 µg per liter in 79 of 138 women (57 percent).Pacific Islanders and Asians had the highest geometric meanlevels of serum ferritin and mean transferrin saturation despitehaving the lowest prevalence of C282Y homozygotes. There were364 participants in whom iron overload had not been diagnosed(29 C282Y homozygotes) who had a serum ferritin level greaterthan 1000 µg per liter. Among men, C282Y homozygotes andcompound heterozygotes were more likely to report a historyof liver disease than were participants without HFE mutations.

Conclusions The C282Y mutation is most common in whites, andmost C282Y homozygotes have elevations in serum ferritin levelsand transferrin saturation. The C282Y mutation does not accountfor high mean serum ferritin levels and transferrin saturationvalues in nonwhites.

Source Information

From the Department of Medicine, London Health Sciences Centre, London, Ont., Canada (P.C.A.); the Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C. (D.M.R., B.M.S.); Southern Iron Disorders Center, Birmingham, Ala. (J.C.B.); Epidemiology Division (C.E.M.) and Division of Hematology and Oncology (G.D.M.), Department of Medicine, University of California, Irvine; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (J.H.E., C.L.-F.); Veterans Affairs Long Beach Healthcare System, Long Beach, Calif. (G.D.M.); Department of Medicine, Howard University, Washington, D.C. (F.W.D., V.R.G.); Departments of Microbiology, Medicine, and Epidemiology and International Health, University of Alabama at Birmingham, Birmingham (R.T.A.); Kaiser Permanente Center for Health Research, Portland, Oreg. (E.L.H.), Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada (M.S.); Kaiser Permanente Center for Health Research, Honolulu (J.L.H.); National Human Genome Research Institute, Bethesda, Md. (E.T.); and the Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, Bethesda, Md. (P.S.).

Address reprint requests to Dr. Adams at the Department of Medicine, London Health Sciences Centre, 339 Windermere Rd., London, ON N6A 5A5, Canada, or at padams{at}uwo.ca.

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