Diabetologia

, 39:807

Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY)

  • M. Rewers
  • T. L. Bugawan
  • J. M. Norris
  • A. Blair
  • B. Beaty
  • M. Hoffman
  • R. S. McDuffie
  • R. F. Hamman
  • G. Klingensmith
  • G. S. Eisenbarth
  • H. A. Erlich
Original

Summary

Autoimmunity causing insulin-dependent diabetes mellitus (IDDM) begins in early childhood due to interactions between genes and unknown environmental factors that may be identified through follow-up of a large cohort of genetically susceptible children. Such a cohort has been established using a simple and rapid cord blood screening for HLA alleles. The DRB1 and DQB1 second exon sequences were co-amplified using the polymerase chain reaction and hybridized with single and pooled sequence-specific oligonucleotide probes. Four individual probes were used to detect the susceptibility alleles DRB1*03, DRB1*04, and DQBl*0302 as well as the usually protective DRB1*15/16 (DR2) alleles. In addition, pooled probes allow the distinction of DR3/3 from the DR3/x genotype (where x is neither DR2, 3, nor 4) and DR4/4 from DR4/x. Among 5000 newborns from the general Denver population, we have found the high-risk genotype (DRBl*03/ DRB1*04, DQBl*0302) to be present in 2.4% of non-Hispanic whites, 2.8% of Hispanics, and 1.6% of African Americans. The moderate-risk genotypes (DRB1*04, DQBl*0302/DRBl*04, DQB1*0302, DRB1*04, DQBl*0302/x, or DRBl*03/DRBl*03) are present in 17 % of American non-Hispanic whites, 24% of Hispanics and in 10% of African Americans. These results demonstrate the feasibility of a large-scale newborn screening for genes associated with IDDM. The ultimate role for such a screening in future routine prediction and prevention of IDDM will depend on the availability of an effective and acceptable form of clinical intervention.

Keywords

Insulin-dependent diabetes mellitus HLA class II alleles newborn screening autoimmunity 

Abbreviations

IDDM

Insulin-dependent diabetes mellitus

PCR

polymerase chain reaction

SSO

sequence-specific oligonucleotide

DAISY

Diabetes Autoimmunity Study in the Young

HRP

horseradish peroxidase

TMB

tetramethyl ben-zidine

SSPE

saline-sodium phosphate-EDTA

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • M. Rewers
    • 1
  • T. L. Bugawan
    • 2
  • J. M. Norris
    • 1
  • A. Blair
    • 2
  • B. Beaty
    • 1
  • M. Hoffman
    • 1
  • R. S. McDuffie
    • 4
  • R. F. Hamman
    • 1
  • G. Klingensmith
    • 3
  • G. S. Eisenbarth
    • 3
  • H. A. Erlich
    • 2
  1. 1.Department of Preventive Medicine and BiometricsUniversity of Colorado, School of MedicineDenverUSA
  2. 2.Human Genetics DepartmentRoche Molecular Systems, Inc.AlamedaUSA
  3. 3.Barbara Davis Center for Childhood DiabetesDenverUSA
  4. 4.Department of Obstetrics and GynecologyKaiser Permanente and St. Joseph’s HospitalDenverUSA

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