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Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY)
M Rewers1, T L Bugawan, J M Norris
1Department of Preventive Medicine and Biometrics, University of Colorado, School of Medicine, Denver 80262, USA.
Insights
Newborn screening for human leukocyte antigen (HLA) genes can identify children at high risk for developing autoimmune insulin-dependent diabetes mellitus (IDDM). This genetic screening method is feasible for large populations, paving the way for potential early prediction and prevention strategies.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Autoimmune insulin-dependent diabetes mellitus (IDDM) originates in childhood, driven by genetic and environmental factors.
- Identifying genetically susceptible children is crucial for understanding IDDM's etiology.
- Human leukocyte antigen (HLA) alleles are key genetic markers for IDDM susceptibility.
Purpose of the Study:
- To establish a cohort of genetically susceptible children using cord blood screening for HLA alleles.
- To assess the feasibility of large-scale newborn screening for IDDM-associated genes.
- To determine the prevalence of high-risk and moderate-risk HLA genotypes in diverse newborn populations.
Main Methods:
- Cord blood samples from newborns were screened for specific HLA DRB1 and DQB1 alleles.
- Polymerase chain reaction (PCR) and sequence-specific oligonucleotide (SSO) probes were employed for HLA typing.
- High-risk (DRB1*03/DRB1*04, DQB1*0302) and moderate-risk genotypes were identified and quantified.
Main Results:
- The high-risk genotype was found in 2.4% of non-Hispanic whites, 2.8% of Hispanics, and 1.6% of African Americans among 5000 newborns.
- Moderate-risk genotypes were present in 17% of non-Hispanic whites, 24% of Hispanics, and 10% of African Americans.
- The study demonstrated the feasibility of large-scale newborn screening for IDDM-associated HLA genes.
Conclusions:
- Newborn HLA screening for IDDM susceptibility is technically feasible.
- The prevalence of high-risk genotypes varies across different ethnic groups.
- Future clinical intervention strategies are necessary to realize the full potential of genetic screening for IDDM prevention.
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.