Advances in the search for psoriasis susceptibility genes

Psoriasis (PS) is a common skin disorder affecting approximately 2% of the Caucasian population. Despite the established influence of several environm ental factors, epidemiological data and twin studies have long demonstrated a genetic basis for psoriasis susceptibility. Moreover an association betw een PS and HLA-Cw6 has been reported in different ethnic groups. In recent years, the availability of statistical methods for complex disease linkage analysis has prompted many researchers to carry out genome-wide scans. Thei r results have been conflicting and linkage replication has seldom been doc umented. However, a few chromosome regions have been confirmed in independe nt studies. In particular, compelling evidence supports the existence of a susceptibility locus within the HLA region. Moreover, loci on chromosomes 1 7q and 1q have been reported in at least two independent genome scans. Seve ral groups have undertaken the refinement of regions identified during geno me scans, using linkage disequilibrium data. This approach has allowed the fine mapping of the 6p21 locus, now restricted to a 60-kb genomic segment. As critical regions get smaller, candidate gene analysis becomes an attract ive approach. So far, three genes have been extensively investigated: S100A 7 on chromosome Iq and CDSN and HCR on chromosome 6p21. Even though several SNPs have been identified within these genes, none of them seems to meet t he requirement needed to prove an involvement in PS pathogenesis. These cri teria include association replication in different populations and function al studies of SNP biological significance. Thus, only a collaborative and m ultidisciplinary approach will allow the identification of PS susceptibilit y genes. (C) 2000 Academic Press.