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

Abstract

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.

• Authors: Jan E Van Autreve, Bobby P C Koeleman, Erik Quartier, Folefac Aminkeng, Ilse Weets, Frans K Gorus, Bart J R Van der Auwera, Belgian Diabetes Registry
• Journal: Human immunology (Hum Immunol) 2006 Jan-Feb Vol. 67 Issue 1-2 Pg. 94-101 ISSN: 0198-8859 [Print] United States
• PMID: 16698430 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• HLA-DQ Antigens
• HLA-DQ alpha-Chains
• HLA-DQ beta-Chains
• HLA-DQA1 antigen
• HLA-DQB1 antigen
• Histocompatibility Antigens Class I
• MHC class I-related chain A

Topics

• Adolescent
• Adult
• Autoantibodies (blood)
• Belgium (epidemiology)
• Cell Membrane (genetics, metabolism)
• Child
• Diabetes Mellitus, Type 1 (epidemiology, genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease (epidemiology, genetics)
• HLA-DQ Antigens (genetics)
• HLA-DQ alpha-Chains
• HLA-DQ beta-Chains
• Histocompatibility Antigens Class I (genetics)
• Humans
• Islets of Langerhans (immunology)
• Male
• Molecular Epidemiology
• Polymorphism, Genetic