Corneodesmosin gene polymorphism demonstrates strong linkage disequilibrium with HLA and association with psoriasis vulgaris

Corneodesmosin (CD) is thought to play a key role in corneocyte cohesion, a nd its proteolysis appears to be a major event in the process of desquamati on. Recently it was shown that CD is encoded by the S-gene, which is locate d approximately 160 kb telomeric of HLA-C. In the present study, the role o f CD in the genetics of psoriasis vulgaris was studied in greater detail. T he second exon of the CD gene was sequenced in 86 HLA-typed individuals fro m 13 psoriasis multiplex families. A total of 11 silent dimorphisms and 7 v ariants resulting in amino acid substitutions were found. Pedigree analysis showed that these variants could be grouped into 7 alleles, encoding 6 dif ferent amino acid sequences. These alleles are in strong linkage disequilib rium with HLA-B and -C, indicating that the polymorphism of the CD gene is ancient and well conserved rather than sporadic. One allele at the CD locus , designated CD2, displayed strong linkage disequilibrium with HLA-Cw6, the HLA allele most prominently associated with psoriasis. CD2 demonstrated a greater relative risk than Cw6 (3.4 vs. 2.5, not significant) and higher si gnificant transmission disequilibrium with psoriasis than any of the invest igated HLA-alleles. Due to its biologic function, cellular location and dis ease association, the CD gene appears to be an excellent candidate gene for PSORS1, the HLA-linked determinant of psoriasis vulgaris.