The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C.

A methionine/valine polymorphism at amino acid 129 of the major histocompatibility complex class I chain-related gene A (MICA-129) categorizes alleles into strong and weak binders of the natural killer (NK) and T-cell receptor NKG2D. We investigated whether MICA-129 is differentially associated with skin and joint manifestations of psoriatic disease (PsD) independently of human leukocyte antigen (HLA)-C and HLA-B in patients and controls from Toronto and St. John's. The MICA-129 methionine (Met) allele, particularly Met/Met homozygosity, was strongly associated with both cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) independently of HLA-B and HLA-C in Toronto patients, and was also associated with PsA in St. John's patients, but with no additional effect of Met/Met homozygosity. No association remained after adjustment for HLA alleles in St. John's patients. MICA-129 was not associated with PsA when compared with PsC. We conclude that MICA-129 is a marker of skin manifestations of PsD that is independent of HLA class I in Toronto patients.