title: Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY).
abstract: 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 DQB1*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 (DRB1*03/ DRB1*04, DQB1*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, DQB1*0302/DRB1*04, DQB1*0302, DRB1*04, DQB1*0302/x, or DRB1*03/DRB1*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.
authors.affiliation: Department of Preventive Medicine and Biometrics, University of Colorado, School of Medicine, Denver 80262, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rewers
authors.forename: T L
authors.initials: TL
authors.lastname: Bugawan
authors.forename: J M
authors.initials: JM
authors.lastname: Norris
authors.forename: A
authors.initials: A
authors.lastname: Blair
authors.forename: B
authors.initials: B
authors.lastname: Beaty
authors.forename: M
authors.initials: M
authors.lastname: Hoffman
authors.forename: R S
authors.initials: RS
authors.lastname: McDuffie
authors.forename: R F
authors.initials: RF
authors.lastname: Hamman
authors.forename: G
authors.initials: G
authors.lastname: Klingensmith
authors.forename: G S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: H A
authors.initials: HA
authors.lastname: Erlich
mesh_terms: D044466:Asian People; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D044383:Black People; D015331:Cohort Studies; D003120:Colorado / Q000453:epidemiology; D017931:DNA Primers / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000517:prevention & control*; D005312:Fetal Blood / Q000276:immunology; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000097:blood*; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008403:Mass Screening / Q000592:standards; D010349:Patient Compliance; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011786:Quality Control; D012307:Risk Factors; D044465:White People; D001741:Black or African American
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D006680:HLA Antigens