title: The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C.
abstract: 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.
authors.affiliation: University of Toronto Psoriatic Arthritis Program, Toronto Western Research Institute, Toronto, Ontario, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Pollock
authors.forename: V
authors.initials: V
authors.lastname: Chandran
authors.forename: F J
authors.initials: FJ
authors.lastname: Pellett
authors.forename: A
authors.initials: A
authors.lastname: Thavaneswaran
authors.forename: L
authors.initials: L
authors.lastname: Eder
authors.forename: J
authors.initials: J
authors.lastname: Barrett
authors.forename: P
authors.initials: P
authors.lastname: Rahman
authors.forename: V
authors.initials: V
authors.lastname: Farewell
authors.forename: D D
authors.initials: DD
authors.lastname: Gladman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens; D015236:HLA-C Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007596:Joints / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology*; D012867:Skin / Q000473:pathology*
chemical_list: D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A