Barker et al. (1) recently proposed two single nucleotide polymorphisms (SNPs) to identify the highest HLA risk for type 1 diabetes. The SNP rs7454108, genotyped by TaqMan probes, tags the HLA haplotype DR4-DQA1*0301-DQB1*0302 (DR4-DQ8), whereas rs2040410, genotyped using PCR–restriction enzyme digestion, tags DR3-DQA1*0501-DQB1*0201 (DR3-DQ2.5). The initial role of HLA in type 1 diabetes was indicated by association with the HLA-DR3 and -DR4 antigens, but, more recently, the HLA-DQA1 and -DQB1 genes were shown to be more strongly associated with this disease (2,3). Individuals homozygous for DR3-DQ2.5 or DR4-DQ8 have an increased risk of developing type 1 diabetes. The highest-risk genotype is formed by DR3-DQ2.5 and DR4-DQ8 haplotypes, probably due to transcomplementation between HLA-DQA1 and HLA-DQB1 alleles on homologous chromosomes (4,5).

We have recently proposed a set of tagging SNPs for detecting HLA risk alleles in celiac disease that can also be used for detecting type 1 diabetes risk (6). Among the known HLA variants that confer risk of celiac disease are the HLA-DQ2.5 and -DQ8 haplotypes, which are the same risk factors as those attributed to type 1 diabetes. Two tagging SNPs were used to predict these heterodimers, and both can be typed using TaqMan technology. The first, tagging HLA-DQ8, is the same SNP as that used by Barker et al. For HLA-DQ2.5, SNP rs2187668 was used, and it is a perfect proxy of SNP rs2040410 (D′ = 1 and r2 = 1). The tagging SNP rs2187668 showed an overall sensitivity of 1.000, a specificity of 0.999, and a positive predictive value of 0.998 (6). Using both tagging SNPs rs7454108 and rs2187668, it will be possible to predict whether an individual is homozygous DQ2.5, homozygous DQ8, or heterozygous DQ2.5/DQ8.

The TaqMan technique used in both studies (1,6) is cost-effective and time saving when applied to large research cohorts, high-risk groups, and population screening studies. This method can also be useful in other disorders, such as systemic lupus erythematosus, rheumatoid arthritis, and other HLA DR3-DQ2–or DR4-DQ8–associated diseases.

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.

No potential conflicts of interest relevant to this article were reported.

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