SKALP ELAFIN GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH PUSTULAR FORMS OF PSORIASIS/

Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear le ukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known a s el afin, is a potent inhibitor of human leukocyte elastase and prote inase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein l evel, SKALP is significantly decreased in lesional skin of patients wi th pustular psoriasis compared with plaque-type psoriasis. This findin g raised the possibility that SKALP could be one of the candidate gene s for pustular forms of psoriasis. We therefore performed single stran d conformation polymorphism (SSCP) analysis on the SKALP gene to scree n for mutations/polymorphisms in the exons of 30 patients with plaque- type psoriasis, 15 patients with pustular psoriasis and 48 healthy con trols. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threoni ne for alanine in the signal peptide. In the promoter region a dinucle otide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that the re is no allelic association between pustular psoriasis and SKALP gene polymorphisms. (C) Munksgaard, 1998.