The enhancer DNase-hypersensitive region 1,2 (HS1,2), a member of the Ig heavy-chain 3' regulatory region (3'RR) cluster, is active in human B cells transfected with reporter genes and in mouse is activated in late maturation. HS1,2-A contains binding sites for several transcription factors. There are four known alleles, that is, (*)1, (*)2, (*)3, and (*)4, which differ in their lengths in transcription factor binding. We showed that in celiac disease the frequency of the (*)2 allele is increased. Both dermatitis herpetiformis (DH) and psoriasis can be associated with different frequencies with celiac disease. Thus, we further investigate the frequency of allele (*)2 in DH, plaque psoriatic, and psoriatic arthritis patients. HS1,2-A allele frequencies were investigated in 37 DH, 61 plaque psoriatic, 28 psoriatic arthritis patients, and 265 healthy donors, age- and sex-matched, from the same geographical area. The frequency of the (*)2 allele changes from 0.39 in controls to 0.63 in DH, 0.59 in plaque psoriasis and 0.75 in psoriatic arthritis (P between 10(-4)-10(-5)). Our data evidence an increased frequency of the (*)2 allele of HS1,2-A in these cutaneous immune-related disorders. We suggest a related genetic predisposition in these pathogeneses.