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. 2008 Nov;57(11):3152-5.
doi: 10.2337/db08-0605. Epub 2008 Aug 11.

Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening

Jennifer M Barker  1 , Taylor M Triolo, Theresa A Aly, Erin E Baschal, Sunanda R Babu, Adam Kretowski, Marian J Rewers, George S Eisenbarth
Affiliations

Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening

Jennifer M Barker et al. Diabetes. 2008 Nov.

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.

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Figures

FIG. 1.
FIG. 1.
Location of SNPs (♦) in relation to classical HLA loci (A) and HLA-DRB1 and -DQB1 loci (B). Numbers are distance in megabase (Mb) pairs from the telomere.
FIG. 2.
FIG. 2.
Proposed algorithm for identifying subjects with DR3/4-DQ8 with SNP testing.
See this image and copyright information in PMC

Comment in

References

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