MICA is associated with type 1 diabetes in the Belgian population, independent of HLA-DQ.

To ascertain association of MICA with type 1 diabetes (T1D) in the Belgian population, well-characterized antibody-positive patients were analyzed for MICA transmembrane gene polymorphism in both an association study and a nuclear family study. The frequency of MICA5 was significantly increased in the T1D patient group (18%) compared with the control population (12%, OR=1.6, pc<10(-3)), whereas MICA9 was decreased (11% versus 16%, OR=0.7, pc<0.01). A p value<10(-3) for the association of MICA conditional on HLA class II and p=0.01 for the conditional extended transmission disequilibrium test were obtained, indicating that MICA is associated with type 1 diabetes, independent of HLA-DQ. Analysis of estimated extended HLA-DQ-MICA haplotypes revealed individual effects of MICA alleles. The most significant effect was seen for MICA5 on the HLA-DQA1*03-DQB1*0302-MICA haplotype (OR=2.5, p<10(-3)). A significant protective effect was seen for the combination of DQA1*01-DQB1*0602/3 and MICA5.1 (OR=0.3, p<10(-3)). However, patients stratified according to the presence or absence of the different MICA alleles did not differ in terms of age at onset, sex, or other diabetes-related clinical and epidemiological data. In conclusion, MICA is associated with type 1 diabetes in the Belgian population and the observed association does not result from the HLA-DQ associated risk.