Capture of Type 1 Diabetes–Susceptible HLA DR-DQ Haplotypes in Japanese Subjects Using a Tag Single Nucleotide Polymorphism

OBJECTIVE To identify type 1 diabetes-susceptible HLA DR-DQ haplotypes using tag single nucleotide polymorphisms (SNPs) and to estimate the disease risk using these tag SNPs. RESEARCH DESIGN AND METHODS Five tag SNPs were typed in a total of 211 Japanese subjects including 201 patients with type 1 diabetes who had already been typed for HLA-DRB1, -DQA1, and -DQB1 alleles and 300 control subjects. RESULTS Tag SNP rs2395185 captured haplotypes involving all DR4 specificities and DR9 specificity with a sensitivity of 98.5% and specificity of 94.9%. Using the T allele of rs2395185, we obtained an odds ratio (95% CI) of 2.87 (2.21-3.74) for type 1 diabetes. In addition, rs3129888 captured haplotypes involving HLA-DRB1*0802 with a sensitivity of 92.3% and specificity of 98.9%. CONCLUSIONS Typing of two tag SNPs (rs2395185 and rs3129888) may be useful for the screening of Japanese subjects at genetic risk of type 1 diabetes.