Major histocompatibility complex class I chain-related gene A polymorphisms and extended haplotypes are associated with familial alopecia areata

Alopecia areata (AA) is characterized by hair loss in patches and may progress to total loss of scalp hair, or total loss of scalp and body hair. The major histocompatibility complex (HLA) is associated with susceptibility to AA, as well as other autoimmune diseases. In addition to HLA molecules, non-HLA molecules including the major histocompatibility complex class I chain-related gene A (MICA), a stress-inducible antigen, are also associated with several autoimmune diseases. To investigate associations between AA and the HLA loci, two genes and eight microsatellite markers spanning the HLA region were genotyped. MICA*6 was significantly associated with all phenotypes of AA (P = 0.0083), whereas MICA*5.1 was significantly associated with patchy AA (P = 0.029). Extended haplotype analysis shows the significant associations of haplotypes HLA-DQ1-DR6-MICA*5.1 (P = 0.004) and HLA-DQB1*0201-DR3-MICA*5.1 (P = 0.009) with AA. These results suggest that MICA is both a potential candidate gene and part of an extended HLA haplotype that may contribute to susceptibility to and severity of AA.