Capture of type 1 diabetes-susceptible HLA DR-DQ haplotypes in Japanese subjects using a tag single nucleotide polymorphism

Diabetes Care. 2010 Jan;33(1):162-4. doi: 10.2337/dc09-1210. Epub 2009 Oct 16.

Abstract

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.

MeSH terms

  • Adult
  • Asian People / genetics
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • HLA-DQ Antigens / genetics*
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Polymorphism, Single Nucleotide / physiology*
  • Young Adult

Substances

  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains