Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Letters: Observations

The Role of Hemochromatosis C282Y and H63D Gene Mutations in Type 2 Diabetes

Findings from the Rotterdam Study and meta-analysis

  1. Omer T. Njajou, PHD1,
  2. Behrooz Z. Alizadeh, MD1,
  3. Norbert Vaessen, MD, PHD12,
  4. Jeannete Vergeer, BSC1,
  5. Jeannine Houwing-Duistermaat, PHD1,
  6. Albert Hofman, MD, PHD1,
  7. Huibert A.P. Pols, MD, PHD12 and
  8. Cornelia M. van Duijn, MD, PHD1
  1. 1Genetic Epidemiology Unit, Department of Epidemiology & Biostatistics, Rotterdam, the Netherlands
  2. 2Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
    Diabetes Care 2002 Nov; 25(11): 2112-2113. https://doi.org/10.2337/diacare.25.11.2112-a
    PreviousNext
    • Article
    • Info & Metrics
    • PDF
    Loading

    Findings from the Rotterdam Study and meta-analysis

    Diabetes is a disease commonly found in patients with hemochromatosis (1). The hemochromatosis C282Y and H63D mutations in the HFE gene are associated with increased iron stores (2), which in turn are associated with glucose intolerance and insulin resistance (3). Whether these HFE mutations play an important role in the pathogenesis of type 2 diabetes is still a matter of controversy.

    We have studied the frequencies of the C282Y and H63D mutations in 254 subjects with glucose intolerance, 220 patients with type 2 diabetes, and 595 normoglycemic individuals (control subjects), all derived from a population-based cohort study (Rotterdam Study) (4). Glucose levels were measured by the hexokinase method in fasting and postload serum samples, and participants were classified as diabetic, glucose intolerant, or normoglycemic (4). Genotyping for the C282Y and H63D mutations was carried out as previously described (5).

    In our population-based sample, we observed that 26 (10.5%) subjects with glucose intolerance, 24 (11.0%) with type 2 diabetes, and 61 (10.6%) control subjects were carriers of the C282Y mutation. For the H63D mutation, 65 (26.0%) glucose-intolerant subjects, 56 (25.7%) type 2 diabetic patients, and 168 (28.5%) control subjects were carriers. Also, the number of homozygotes for the H63D mutation in glucose-intolerant patients (1.7%) and in type 2 diabetic patients (1.8%) was similar to that seen in control subjects (1.5%). There were too few homozygotes for the C282Y mutation among glucose-intolerant (n = 2) and diabetic patients (n = 1) to yield reliable results.

    Because of the low frequency of the C282Y mutation, we reanalyzed all published association studies between the HFE mutations and type 2 diabetes in a meta-analysis. Our meta-analysis included 12 studies for the C282Y mutation and 8 studies for the H63D mutation. There was no evidence for heterogeneity (χ2= 18.5, 11, P = 0.07) between studies. Of 2,630 type 2 diabetic patients, 225 (8.6%) were carriers of the C282Y mutations compared with 327 of 3,437 control subjects (9.5%), yielding an odds ratio (OR) (95% CI) of 1.0 (0.8–1.4), suggesting no association between C282Y and the risk of diabetes. When studying the C282Y homozygosity, there was no significant association to diabetes (1.1 [0.6–2.3]). For the H63D mutation, 559 type 2 diabetic patients of 1,889 (29.6%) and 690 control subjects of 2,524 (27.3%) were carriers, yielding an OR of 1.1 (1.0–1.3). The frequency of H63D homozygosity was modestly increased (1.2 [1.1–2.3]) in type 2 diabetic patients, suggesting no major effect of the H63D mutation on type 2 diabetes.

    In conclusion, there was no evidence for an increased frequency of the C282Y or H63D mutations in patients with impaired glucose intolerance or type 2 diabetes in our population-based sample or in the meta-analysis. Also, the findings of our meta-analysis suggest that the role of HFE mutations in the pathogenesis of diabetes in the general population is limited.

    Footnotes

    • Address correspondence to Omer T. Njajou, Genetic Epidemiology Unit, Department of Epidemiology & Biostatistics, P.O. Box 1738, Rotterdam, 3000 DR, the Netherlands. E-mail: njajou{at}lycos.com.

    • DIABETES CARE

    References

    1. ↵
      Phelps G, Chapman I, Hall P, Braund W, Mackinnon M: Prevalence of genetic hemochromatosis among diabetic patients. Lancet 8657:233–234, 1989
      OpenUrl
    2. ↵
      Whitfield JB, Cullen LM, Jazwinska EC, Powell LW, Heath AC, Zhu G, Duffy DL, Martin NG: Effects of HFE C282Y and H63D polymorphism and polygenic background on iron stores in a large community sample of twins. Am J Hum Genet 66:1246–1258, 2000
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      Tuomainen TP, Nyyssonen K, Salonen R, Tervahauta A, Korpela H, Lakka T, Kaplan GA, Salonen JT: Body iron stores are associated with serum insulin and blood glucose concentrations: population study in 1,013 eastern Finnish men. Diabetes Care 20:426–428, 1997
      OpenUrlAbstract/FREE Full Text
    4. ↵
      Baan CA, Stolk RP, Grobbee DE, Witteman JCM, Feskens EJM: Physical activity in elderly subjects with impaired glucose tolerance and newly diagnosed diabetes mellitus. Am J Epid 149:219–227, 1999
      OpenUrlAbstract/FREE Full Text
    5. ↵
      Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Wolff RK, et al: A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis. Nat Genet 13: 399–408, 1996
    PreviousNext
    Back to top
    Diabetes Care: 25 (11)

    In this Issue

    November 2002, 25(11)
    • Table of Contents
    • About the Cover
    • Index by Author
    Sign up to receive current issue alerts
    View Selected Citations (0)
    Print
    Download PDF
    Article Alerts
    Sign In to Email Alerts with your Email Address
    Email Article

    Thank you for your interest in spreading the word about Diabetes Care.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    The Role of Hemochromatosis C282Y and H63D Gene Mutations in Type 2 Diabetes
    (Your Name) has forwarded a page to you from Diabetes Care
    (Your Name) thought you would like to see this page from the Diabetes Care web site.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Citation Tools
    The Role of Hemochromatosis C282Y and H63D Gene Mutations in Type 2 Diabetes
    Omer T. Njajou, Behrooz Z. Alizadeh, Norbert Vaessen, Jeannete Vergeer, Jeannine Houwing-Duistermaat, Albert Hofman, Huibert A.P. Pols, Cornelia M. van Duijn
    Diabetes Care Nov 2002, 25 (11) 2112-2113; DOI: 10.2337/diacare.25.11.2112-a

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    Add to Selected Citations
    Share

    The Role of Hemochromatosis C282Y and H63D Gene Mutations in Type 2 Diabetes
    Omer T. Njajou, Behrooz Z. Alizadeh, Norbert Vaessen, Jeannete Vergeer, Jeannine Houwing-Duistermaat, Albert Hofman, Huibert A.P. Pols, Cornelia M. van Duijn
    Diabetes Care Nov 2002, 25 (11) 2112-2113; DOI: 10.2337/diacare.25.11.2112-a
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Jump to section

    • Article
      • Footnotes
      • References
    • Info & Metrics
    • PDF

    Related Articles

    Cited By...

    More in this TOC Section

    • Weight Gain and Gestational Diabetes Mellitus Is a Sensitive Issue
    • Beneficial Effects of a 4-Week Exercise Program on Plasma Concentrations of Adhesion Molecules
    • Malignant Melanoma Misdiagnosed as a Diabetic Foot Ulcer
    Show more Letters: Observations

    Similar Articles

    Navigate

    • Current Issue
    • Standards of Care Guidelines
    • Online Ahead of Print
    • Archives
    • Submit
    • Subscribe
    • Email Alerts
    • RSS Feeds

    More Information

    • About the Journal
    • Instructions for Authors
    • Journal Policies
    • Reprints and Permissions
    • Advertising
    • Privacy Policy: ADA Journals
    • Copyright Notice/Public Access Policy
    • Contact Us

    Other ADA Resources

    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • Scientific Sessions Abstracts
    • Standards of Medical Care in Diabetes
    • BMJ Open - Diabetes Research & Care
    • Professional Books
    • Diabetes Forecast

     

    • DiabetesJournals.org
    • Diabetes Core Update
    • ADA's DiabetesPro
    • ADA Member Directory
    • Diabetes.org

    © 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.