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.
Van Autreve
Jan E
JE
Diabetes Research Center, Molecular Diagnosis Unit, Vrije Universteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Koeleman
Bobby P C
BP
Quartier
Erik
E
Aminkeng
Folefac
F
Weets
Ilse
I
Gorus
Frans K
FK
Van der Auwera
Bart J R
BJ
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001530:Belgium / Q000453:epidemiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A