“Extended” A1, B8, DR3 Haplotype Shows Remarkable Linkage Disequilibrium but Is Similar to Nonextended Haplotypes in Terms of Diabetes Risk

  1. Akane Ide,
  2. Sunanda R. Babu,
  3. David T. Robles,
  4. Tianbao Wang,
  5. Henry A. Erlich,
  6. Teodorica L. Bugawan,
  7. Marian Rewers,
  8. Pamela R. Fain and
  9. George S. Eisenbarth
  1. Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado
  1. Address correspondence and reprint requests to George S. Eisenbarth MD, PhD, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Ave., Box B140, Denver, CO 80262. E-mail: george.eisenbarth{at}


To evaluate potential differential diabetes risk of DR3 haplotypes we have evaluated class I alleles as well as two microsatellites previously associated with differential risk associated with DR3 haplotypes. We found that over one-third of patient DR3 chromosomes consisted of an extended DR3 haplotype, from DQ2 to D6S2223 (DQ2, DR3, D6S273-143, MIC-A5.1, HLA-B8, HLA-Cw7, HLA-A1, and D6S2223-177) with an identical extended haplotype in controls. The extended haplotype was present more frequently (35.1% of autoimmune-associated DR3 haplotypes, 39.4% of control DR3 haplotypes) than other haplotypes (no other haplotype >5% of DR3 haplotypes) and remarkably conserved, but it was not transmitted from parents to affected children more frequently than nonconserved DR3-bearing haplotypes. This suggests that if all alleles are truly identical for the major A1, B8, DR3 haplotype (between A1 and DR3), with different alleles on nonconserved haplotypes without differential diabetes risk, then in this region of the genome DR3-DQ2 may be the primary polymorphisms of common haplotypes contributing to diabetes risk.


  • 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 7, 2005.
    • Received November 5, 2004.
| Table of Contents