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

被引:24
|
作者
Törn, C
Gupta, M
Zake, LN
Sanjeevi, CB
Landin-Olsson, M
机构
[1] Lund Univ, Diabet Lab, Lund, Sweden
[2] Lund Univ, Inst Med, Lund, Sweden
[3] CMM, Dept Mol Med, Stockholm, Sweden
关键词
type; 1; diabetes; HLA; MICA; LADA; risk;
D O I
10.1016/S0198-8859(03)00158-7
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Major histocompatibility complex class I chain-related gene A (MICA) encodes polymorphic, stress-inducible antigens recognized by gammadeltaT 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 MI-CA5.0/5.1 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 I 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. (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Inc.
引用
收藏
页码:902 / 909
页数:8
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