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

Citation
S. Jenisch et al., Corneodesmosin gene polymorphism demonstrates strong linkage disequilibrium with HLA and association with psoriasis vulgaris, TISSUE ANTI, 54(5), 1999, pp. 439-449
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
TISSUE ANTIGENS
ISSN journal
0001-2815 → ACNP
Volume
54
Issue
5
Year of publication
1999
Pages
439 - 449
Database
ISI
SICI code
0001-2815(199911)54:5<439:CGPDSL>2.0.ZU;2-7
Abstract
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.