HLA Genotyping Supports a Nonautoimmune Etiology in Patients Diagnosed With Diabetes Under the Age of 6 Months

  1. Emma L. Edghill1,
  2. Rachel J. Dix2,
  3. Sarah E. Flanagan1,
  4. Polly J. Bingley2,
  5. Andrew T. Hattersley1,
  6. Sian Ellard1 and
  7. Kathleen M. Gillespie2
  1. 1Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K
  2. 2Department of Clinical Science at North Bristol, University of Bristol, Bristol, U.K
  1. Address correspondence and reprint requests to Dr. K.M. Gillespie, Medical School Unit, Southmead Hospital, Bristol BS10 5NB, U.K. E-mail: k.m.gillespie{at}bristol.ac.uk

Abstract

Children with permanent diabetes are usually assumed to have type 1 diabetes. It has recently been shown that there are genetic subgroups of diabetes that are often diagnosed during the neonatal period but may present later. A recent Italian study proposed that type 1 diabetes is rare before 6 months of age. We aimed to examine genetic susceptibility to type 1 diabetes in patients diagnosed with diabetes before the age of 2 years. We analyzed HLA class II genotypes, markers of autoimmune diabetes, in 187 children with permanent diabetes diagnosed at <2 years of age. Of the 79 subjects diagnosed at <6 months of age, 41% (95% CI 0.30–0.51) had type 1 diabetes–associated high-risk genotypes, a proportion similar to that in healthy population control subjects (44%, P = 0.56). This group included 32 patients with mutations in the KCNJ11 gene, which encodes Kir6.2 (44% high-risk HLA class II genotypes), and 47 in whom the etiology of diabetes was unknown (38% high-risk HLA class II genotypes). Of 108 patients diagnosed between 6 and 24 months of age, 93% (0.86–0.99) had high-risk HLA class II genotypes compared with 44% of the population control subjects (P < 0.0001). We conclude that infants diagnosed with diabetes before 6 months of age are unlikely to have autoimmune type 1 diabetes and are most likely to have a monogenic etiology.

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

    DOI: 10.2337/db06-0094

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 13, 2006.
    • Received January 20, 2006.
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