MICA polymorphism in a sample of the São Paulo population, Brazil

Abstract

The major histocompatibility complex (MHC) class I chain-related A (MICA) gene, located near HLA-B, codes for protein products with structural similarities to those of classical MHC class I genes, but which neither bind beta(2)-microglobulin nor present peptide. Expressed predominantly on gastrointestinal and tumour epithelial cells, they are stress-induced and interact with C-type lectin like receptor (NKG2D) on gammadelta, alphabeta CD8+ T cells and natural killer (NK) cells. MICA is highly polymorphic, with 54 extracellular allelic sequences described. We typed 200 healthy subjects in a sample of the São Paulo population by extended polymerase chain reaction-sequence-specific primers (PCR-SSP) to characterize the MICA polymorphism and analysed MICA/HLA-B linkage disequilibrium. The MICA*008 group (g) was predominant (47%), with several HLA-B associations. Rare combinations MICA*008g-HLA-B37, MICA*008g-B72 and MICA*010-HLA-B52 were detected. Given the extent of this polymorphism and its possible relevance for disease association, we determined MICA and HLA-B alleles in 33 Behçet's patients, in an attempt to clarify the associated genetic marker. Our results showed an increase of MICA*006, but not MICA*009, in the patient group (6/33) compared with controls (3/200) (18.2% vs. 1.5%; P(c) = 0.005). Both alleles were always in association with HLA-B51, suggesting that HLA-B is indeed the primary susceptibility locus (P = 0.00008) and that MICA*006 may be an additional risk factor.