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5 September 2000 | Volume 133 Issue 5 | Pages 329-337
Background: The gene that causes most cases of hereditary hemochromatosis is designated HFE. Three mutations exist at this locus at a relatively high gene frequency.
Objective: To determine the gene frequency of the three HFE mutations and to relate genotypes to various clinical and laboratory variables.
Design: Observational study.
Setting: Health appraisal clinic.
Patients: 10 198 adults who registered for health appraisal and consented to DNA examination for hemochromatosis. Consenting patients were slightly older and had attained a slightly higher educational level than nonconsenting patients.
Measurements: Extensive medical history and laboratory tests, including complete blood count, transferrin saturation, and other chemistries; serum ferritin levels; and HFE genotype.
Results: In white participants, the gene frequencies were 0.063 for the C282Y mutation, 0.152 for the H63D mutation, and 0.016 for the S65C mutation. Gene frequencies were lower in other ethnic groups. In participants with HFE mutations, the average serum transferrin saturation and ferritin levels were slightly increased, as were mean hemoglobin levels and mean corpuscular volume. A transferrin saturation of 50% had a sensitivity of only 0.52 (95% CI, 0.345 to 0.686) and a specificity of 0.908 (CI, 0.902 to 0.914) for detection of homozygosity. A ferritin level of 200 µg/L in women and 250 µg/L in men had a sensitivity of 0.70 (CI, 0.540 to 0.854) and a specificity of 0.803 (CI, 0.796 to 0.811). The prevalence of iron deficiency anemia was lower in women who carried HFE mutations.
Conclusions: Screening for transferrin saturation and ferritin levels does not detect all homozygotes for the major hemochromatosis mutation. Heterozygotes for HFE mutations had a lower prevalence of iron deficiency anemia.
Author and Article Information
From The Scripps Research Institute, La Jolla, California; and Kaiser Permanente, San Diego, California.
Acknowledgments: This report is manuscript number 12824-MEM from The Scripps Research Institute. The authors thank Marsha MacDonald, Renee Olson, Tony Mondala, Priscilla Crisler, Carol West, and Naomi Howard for assistance in performing these investigations.
Grant Support: By grant DK53505-02 supplemented with a grant from the Division of Nutrition and Physical Activity, Centers for Disease Control and Prevention, grant RR00833 from the National Institutes of Health, and funds from the Stein Endowment Fund.
Requests for Single Reprints: Ernest Beutler, MD, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; e-mail, beutler{at}scripps.edu.
Requests to Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.
Current Author Addresses: Dr. Beutler, Ms. Gelbart, and Ms. Ho: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037.
Dr. Fellitti: Kaiser Permanente, 7060 Clairemont Mesa Boulevard, San Diego, CA 92111.
Author Contributions: Conception and design: E. Beutler, V. Felitti.
Analysis and interpretation of the data: E. Beutler, V. Felitti, T. Gelbart, N. Ho.
Drafting of the article: E. Beutler.
Critical revision of the article for important intellectual content: E. Beutler, V. Felitti, T. Gelbart.
Final approval of the article: E. Beutler, V. Felitti, T. Gelbart, N. Ho.
Provision of study materials or patients: V. Felitti.
Statistical expertise: E. Beutler, N. Ho.
Obtaining of funding: E. Beutler.
Administrative, technical, or logistic support: E. Beutler, V. Felitti, T. Gelbart, N. Ho.
Collection and assembly of data: E. Beutler, V. Felitti, T. Gelbart, N. Ho. ARTICLE
The Effect of HFE Genotypes on Measurements of Iron Overload in Patients Attending a Health Appraisal Clinic
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