Heterozygosity for MICA5.0/MICA5.1 and HLA-DR3-DQ2/DR4-DQ8 are independent genetic risk factors for latent autoimmune diabetes in adults

Hum Immunol. 2003 Sep;64(9):902-9. doi: 10.1016/s0198-8859(03)00158-7.


Major histocompatibility complex class I chain-related gene A (MICA) encodes polymorphic, stress-inducible antigens recognized by gammadelta T cells within the intestinal epithelium. MICA microsatellite polymorphism has been implicated to be related to different autoimmune diseases. Ninety-eight patients with type 1 diabetes (median age, 35 years; range, 9-89 years and 51 patients with latent autoimmune diabetes (LADA; median age, 48 years; range, 19-79 years) were compared with 113 healthy control patients (median age, 35 years; range, 19-65 years) to study the importance of MICA-microsatellite polymorphism and HLA-DR-DQ as genetic risk factors for diabetes. The different factors were compared univariately and by logistic regression analysis. In the logistic regression model, heterozygosity for MICA5.0/5.1 was a significant risk factor for LADA (odds ratio [OR] = 12; 95% confidence interval [95%CI], 2.5-59) as well as heterozygosity for HLA-DR3-DQ2/DR4-DQ8 (OR = 15; 95%CI, 2.7-84). None of the MICA polymorphisms were related to type 1 diabetes. Heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was a risk factor for type 1 diabetes (OR = 14; 95%CI, 2.9-66) as well as DR4-DQ8/x (OR = 2.8; 95%CI, 1.4-5.9). HLA-DR15-DQ6 was protective for type 1 diabetes (OR = 0.12; 95%CI, 0.015-0.96). We concluded that both heterozygosity for MICA5.0/5.1 and HLA-DR3-DQ2/DR4-DQ8 are separate risk factors for LADA, but that heterozygosity for HLA-DR3-DQ2/DR4-DQ8 and DR4-DQ8 alone are most important for type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Genetic Predisposition to Disease*
  • HLA-DQ Antigens / genetics*
  • HLA-DR Antigens / genetics*
  • HLA-DR3 Antigen / genetics
  • HLA-DR3 Antigen / immunology
  • HLA-DR4 Antigen / genetics
  • Heterozygote
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Middle Aged
  • Multivariate Analysis


  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • HLA-DR Antigens
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A