Screening for Iron Overload: Lessons from the HEmochromatosis and IRon Overload Screening (HEIRS) Study

Author:

Adams Paul C1,Barton James C2,McLaren Gordon D3,Acton Ronald T4,Speechley Mark5,McLaren Christine E6,Reboussin David M7,Leiendecker-Foster Catherine8,Harris Emily L9,Snively Beverly M7,Vogt Thomas10,Sholinsky Phyliss11,Thomson Elizabeth12,Dawkins Fitzroy W13,Gordeuk Victor R10,Eckfeldt John H8

Affiliation:

1. Department of Medicine, London Health Sciences Centre, London, Ontario, Canada

2. Southern Iron Disorders Center, Birmingham, Alabama, USA

3. VA Long Beach Healthcare System, Long Beach, and Univeristy of California, Irvine, California, USA

4. Department of Microbiology, University of Alabama, Birmingham, Alabama, USA

5. University of Western Ontario, London, Ontario, Canada

6. Department of Epidemiology, University of California, Irvine, California, USA

7. Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

8. Departments of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA

9. Translational Genomics Research Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA

10. Kaiser Permanente Center for Health Research, Honolulu, Hawaii, USA

11. Department of Epidemiology and Biostatistics, Epidemiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA

12. National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA

13. Department of Medicine, Howard University, Washington DC, USA

Abstract

BACKGROUND: The HEmochromatosis and IRon Overload Screening (HEIRS) Study provided data on a racially, ethnically and geographically diverse cohort of participants in North America screened from primary care populations.METHODS: A total of 101,168 participants were screened by testing forHFEC282Y and H63D mutations, and measuring serum ferritin concentration and transferrin saturation. In the present review, lessons from the HEIRS Study are highlighted in the context of the principles of screening for a medical disease as previously outlined by the World Health Organization.RESULTS: Genetic testing is well accepted, with minimal risk of discrimination. Transferrin saturation has high biological variability and relatively low sensitivity to detectHFEC282Y homozygotes, which limits its role as a screening test. Symptoms attributable toHFEC282Y homozygosity are no more common in individuals identified by population screening than in control subjects.CONCLUSIONS: Generalized population screening in a primary care population as performed in the HEIRS Study is not recommended. There may be a role for focused screening in Caucasian men, with some debate regarding genotyping followed by phenotyping, or phenotyping followed by genotyping.

Publisher

Hindawi Limited

Subject

Gastroenterology,General Medicine

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