Heterozygosity for MICA5.0/MICA5.1 and HLA-DR3-DQ2/DR4-DQ8 are independent genetic risk factors for latent autoimmune diabetes in adults.
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.
Törn
Carina
C
Institution of Medicine, Lund University, Lund, Sweden. carina.torn@med.lu.se
Gupta
Manu
M
Nikitina Zake
Liene
L
Sanjeevi
Carani B
CB
Landin-Olsson
Mona
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000235:genetics; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A