FAMILIAL JUVENILE-ONSET PSORIASIS IS ASSOCIATED WITH THE HUMAN-LEUKOCYTE ANTIGEN (HLA) CLASS-I SIDE OF THE EXTENDED HAPLOTYPE STERISK-0701-DQA1-ASTERISK-0201-DQB1-ASTERISK-0303 - A POPULATION-BASED AND FAMILY-BASED STUDY

To further evaluate the nature of the HLA association with psoriasis, HLA haplotypes of 60 patients with type I (early onset, positive famil y history) and 30 patients with type II Gate onset, no family history) psoriasis were investigated by polymerase chain reaction sequence-spe cific oligonucleotide hybridization (HLA class II) and serology (HLA c lass I), Ethnically matched blood donors (146) served as controls, In type I, but not type II psoriasis, the Caucasian HLA extended haplotyp e (EH) Cw6-B57-DRB10701-DQA1*0201-DQB1*0303 named according to the B allele EH-57.1 was highly significantly overrepresented (p(cor.) = 0.0 0021). This particular EH was present in 35% of type I psoriatics but only 2% bf controls, EH-57.1+ individuals therefore carry a 26 times h igher risk of developing type I psoriasis than individuals who are EH- 57.1-negative. Further analysis of individual HLA alleles revealed tha t within EH-57.1, HLA class I antigens (Cw6-B57) were associated to a much higher extent with type I psoriasis than the HLA class II alleles (DRB10701-DQA1*0201-DQB1*0303). Pedigree analysis of three multiply affected families over three generations revealed a cosegregation of d isease with EH-57.1. These results strongly suggest that a gene for fa milial psoriasis is associated with the class I side of the extended h aplotype Cw6-B57-DRB10701-DQA1*0201-DQB1*0303.