Original

Diabetologia

, 39:807

First online:

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

  • M. RewersAffiliated withDepartment of Preventive Medicine and Biometrics, University of Colorado, School of Medicine
  • , T. L. BugawanAffiliated withHuman Genetics Department, Roche Molecular Systems, Inc.
  • , J. M. NorrisAffiliated withDepartment of Preventive Medicine and Biometrics, University of Colorado, School of Medicine
  • , A. BlairAffiliated withHuman Genetics Department, Roche Molecular Systems, Inc.
  • , B. BeatyAffiliated withDepartment of Preventive Medicine and Biometrics, University of Colorado, School of Medicine
  • , M. HoffmanAffiliated withDepartment of Preventive Medicine and Biometrics, University of Colorado, School of Medicine
  • , R. S. McDuffieAffiliated withDepartment of Obstetrics and Gynecology, Kaiser Permanente and St. Joseph’s Hospital
  • , R. F. HammanAffiliated withDepartment of Preventive Medicine and Biometrics, University of Colorado, School of Medicine
  • , G. KlingensmithAffiliated withBarbara Davis Center for Childhood Diabetes
    • , G. S. EisenbarthAffiliated withBarbara Davis Center for Childhood Diabetes
    • , H. A. ErlichAffiliated withHuman Genetics Department, Roche Molecular Systems, Inc.

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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