Two Single Nucleotide Polymorphisms Identify the Highest-Risk Diabetes HLA Genotype
Potential for Rapid Screening
- Jennifer M. Barker,
- Taylor M. Triolo,
- Theresa A. Aly,
- Erin E. Baschal,
- Sunanda R. Babu,
- Adam Kretowski,
- Marian J. Rewers and
- George S. Eisenbarth
- From the Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Denver, Colorado
- Corresponding author: Jennifer M. Barker, jennifer.barker{at}uchsc.edu
Abstract
OBJECTIVE—People with the 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 publicly available data on 5,019 subjects from the Type 1 Diabetes Genetic Consortium (T1DGC). Additionally, we analyzed these SNPs in samples from 143 HLA-typed children who participated in 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% (1,173 of 1,191) sensitive and 99.7% (3,815 of 3,828) specific for DR3/4-DQ8. In the DAISY population, the test was 100% (69 of 69) sensitive and 100% (74 of 74) specific. Overall, the sensitivity and specificity for the test were 98.57 and 99.67%, respectively.
CONCLUSIONS—A two-SNP screening test can identify the highest risk heterozygous genotype for type 1 diabetes in a time- and cost-effective manner.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 11 August 2008.
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Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
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- Accepted August 5, 2008.
- Received May 5, 2008.
- DIABETES
