Familial Juvenile Onset Psoriasis Is Associated with the Human Leukocyte Antigen (HLA) Class I side of the Extended Haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303: A Population- And Family-Based Study

Abstract

To further evaluate the nature of the HLA association with psoriasis, HLA haplotypes of 60 patients with type 1 (early onset, positive family history) and 30 patients with type II (late onset, no family history) psoriasis were investigated by polymerase chain reaction sequence-specific oligonucleotide hybridization (HLA class II) and serology (HLA class I). Ethnically matched blood donors (146) served as controls. In type I, but not type II psoriasis, the Caucasian HLA extended haplotype (EH) Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303 named according to the B allele EH-57.1 was highly significantly overrepresented (p cor= 0.00021). This particular EH was present in 35% of type I psoriatics but only 2% of controls. EH-57.1+ individuals therefore carry a 26 times higher risk of developing type I psoriasis than individuals who are EH-57.1-negative Further analysis of individual HLA alleles revealed that 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 (DRB1*0701-DQA1*0201-DQB1* 0303). Pedigree analysis of three multiply affected families over three generations revealed a cosegregation of disease with EH-57.1. These results strongly suggest that a gene for familial psoriasis is associated with the class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303.

A Peculiar Sequence Motif in the Alpha-1-Domain of the HLA-C Molecule in Psoriasis

“…Two groups of research described a supratypic view of the genetic predisposition of type I psoriasis, emphasizing the importance of the extended ancestral haplotype AH 57.1 (Cw6, B57, C4A6, C4B1, DRB1*0701, DQA1*0201, DQB1*0303) for its determination [6, 7]. …”

Parental Segregation of Autoimmunity in Patients with Turner's Syndrome: Preferential Paternal Transmission?

“…In the families studied, we found an association between the presence of autoantibodies and HLA-DR7;DQ2 and HLA-DR7;DQ9 haplotypes, which has been reported to be associated with autoimmune disorders [33,34,35]. No relationship between autoantibodies and GM and KM allotypes or epistatic interaction between HLA and GM genes was observed, as has conversely been demonstrated for other autoimmune disorders [21,36].…”

A possible relationship of human leucocyte antigens with psoriasis vulgaris and geographic tongue

“…It is known that HLA-C*06 is a locus risk for psoriasis that is in linkage disequilibrium with HLA-B*57 39,40 and -DRB1*07 on the extended haplotype HLA-C*06-B*57-DRB1*07, 41 particularly for familial juvenile onset psoriasis. 42 Moreover, Schmitt-E- 43 In our data, the haplotype C*06-B*57-DRB1*07 was detected four times in the control group and seven times in the psoriasis group; this created a risk ratio of 1.91 (P = 0.028). Although LD between C*06 and B*57 or B*58 in our sample B*57 was stronger for psoriasis (OR = 6.05, P = 0.008) than C*06 (OR = 2.78, P = 0.005) and B*58, in geographic tongue, presented OR = 3.46 (P = 0.018) against control and OR = 0.19 (P = 0.012) against psoriasis.…”