NEWBORN SCREENING FOR HLA MARKERS ASSOCIATED WITH IDDM - DIABETES AUTOIMMUNITY STUDY IN THE YOUNG (DAISY)

Autoimmunity causing insulin-dependent diabetes mellitus (IDDM) begins in early childhood due to interactions between genes and unknown envi ronmental factors that may be identified through follow-up of a large cohort of genetically susceptible children. Such a cohort has been est ablished 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 sequen ce-specific oligonucleotide probes. Four individual probes were used t o detect the susceptibility alleles DRB103, DRB1*04, and DQB1*0302 as well as the usually protective DRB115/16 (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 ne wborns from the general Denver population, we have found the high-risk genotype (DRB103/DRB1*04, DQB1*0302) to be present in 2.4% of non-Hi spanic whites, 2.8% of Hispanics, and 1.6% of African Americans. The m oderate-risk genotypes (DRB104, DQB1*0302/DRB1*04, DQB1*0302, DRB1*04 , DQB10302/x, or DRB1*03/DRB1*03) are present in 17% of American non- Hispanic whites, 24% of Hispanics and in 10% of African Americans. The se results demonstrate the feasibility of a large-scale newborn screen ing for genes associated with IDDM. The ultimate role for such a scree ning in future routine prediction and prevention of IDDM will depend o n the availability of an effective and acceptable form of clinical int ervention.