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Diabetes Publish Ahead of Print published online ahead of print August 11, 2008
DOI: 10.2337/db08-0605
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Original Research

Two Single Nucleotide Polymorphisms Identify Highest-Risk Diabetes Human Leukocyte Antigen Genotype: Potential for Rapid Screening

Jennifer M. Barker, MD, Taylor M. Triolo, BS, Theresa A. Aly, MD, PhD, Erin E. Baschal, BA, Sunanda R. Babu, PhD, Adam Kretowski, MD, Marian J. Rewers, MD PhD, and George S. Eisenbarth, MD, PhD

OBJECTIVE: People with the human leukocyte antigen (HLA) genotype DRB1*0301-DQA1*0501-DQB1*0201/DRB1*04-DQA1*0301-DQB1*0302 (DR3/4-DQ8) are at the highest risk of developing type 1 diabetes. We sought to find an inexpensive, rapid test to identify DR3/4-DQ8 subjects using two single nucleotide polymorphisms (SNPs).

RESEARCH DESIGN AND METHODS: SNPs rs2040410 and rs7454108 were associated with DR3-DQB1*0201 and DR4-DQB1*0302. We correlated these SNPs with HLA genotypes and with publically available data of 5019 subjects from the Type 1 Diabetes Genetic Consortium (T1DGC). Additionally, we analyzed these SNPs in samples from 143 HLA-typed children of the Diabetes Autoimmunity Study of the Young (DAISY) using Taqman® probes (rs7454108) and restriction digest analysis (rs2040410).

RESULTS: With a simple combinatorial rule, the SNPs of interest identified the presence or absence of the DR3/4-DQ8 genotype. A wide variety of genotypes were tested for both SNPs. In T1DGC samples, the two SNPs were 98.5% (1173/1191) sensitive and 99.7% (3815/3828) specific for DR3/4-DQ8. In the DAISY population the test was 100% (69/69) sensitive and 100% (74/74) specific. Overall, the sensitivity for the test was 98.57% and was 99.67% specific.

CONCLUSIONS: A two SNP screening test can identify the highest risk heterozygous genotype for type 1 diabetes, in a time- and cost-effective manner.

Correspondence: jennifer.barker{at}uchsc.edu


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Copyright © 2008 by the American Diabetes Association.