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, and its proteolysis appears to be a major event in the process of desquamation. Recently it was shown that CD is encoded by the S-gene, which is located approximately 160 kb telomeric of HLA-C. In the present study, the role of CD in the genetics of psoriasis vulgaris was studied in greater detail. The second exon of the CD gene was sequenced in 86 HLA-typed individuals from 13 psoriasis multiplex families. A total of 11 silent dimorphisms and 7 variants resulting in amino acid substitutions were found. Pedigree analysis showed that these variants could be grouped into 7 alleles, encoding 6 different amino acid sequences. These alleles are in strong linkage disequilibrium 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 significant transmission disequilibrium with psoriasis than any of the investigated HLA-alleles. Due to its biologic function, cellular location and disease association, the CD gene appears to be an excellent candidate gene for PSORS1, the HLA-linked determinant of psoriasis vulgaris.
Jenisch
S
S
Department of Immunology, University of Kiel, Germany. jenisch@immunologie.uni-kiel.de
Koch
S
S
Henseler
T
T
Nair
R P
RP
Elder
J T
JT
Watts
C E
CE
Westphal
E
E
Voorhees
J J
JJ
Christophers
E
E
Krönke
M
M
D000483:Alleles; D015331:Cohort Studies; D005091:Exons; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology
C109656:CDSN protein, human; D006023:Glycoproteins; D006680:HLA Antigens; D036341:Intercellular Signaling Peptides and Proteins