Evidence that a locus for familial psoriasis maps to chromosome 4q

Abstract

Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.

Combined segregation and linkage analysis of HLA markers in familial psoriasis

“…21 However, some of these scans found no evidence for linkage to HLA. 15,16,20 We subsequently showed that the evidence for linkage to HLA is markedly increased when linkage disequilibrium information is taken into account. 11,12 Recently, PSORS1 has been fine-mapped to the vicinity of HLA-C by linkage disequilibrium mapping.…”

Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden

“…28 A recessive model with an estimated penetrance of 80% and a gene frequency of 0.25 (deduced from earlier studies, 6,11 ) and a dominant model with an estimated penetrance of 70% and a gene frequency of 1.3% 17 were used.…”

“…Replication studies have been reported supporting the locus on 17q, 13,14 whereas other studies fail to confirm it. 15, 16 Matthews et al 17 reported a second psoriasis gene location on chromosome 4q using a dominant model with reduced penetrance. No other study has been able to confirm this locus.…”

Cytogenetic analysis of 477 psoriatics revealed an increased frequency of aberrations involving chromosome region 11q

“…2 The genetic linkage analyses presented so far also indicate several possible non-HLA gene locations, all of which have not been confirmed. [2][3][4][5][6] Two of these studies using a few large pedigrees presented data suggesting a psoriasis susceptibility locus on 17q and 4q respectively. 3,4 Trembath et al 2 recently reported a genome scan of 66 affected sib pairs in which four potential psoriasis susceptibility loci were identified, on chromosome 2p, 6p (HLA region), 8q and 20p.…”

“…[2][3][4][5][6] Two of these studies using a few large pedigrees presented data suggesting a psoriasis susceptibility locus on 17q and 4q respectively. 3,4 Trembath et al 2 recently reported a genome scan of 66 affected sib pairs in which four potential psoriasis susceptibility loci were identified, on chromosome 2p, 6p (HLA region), 8q and 20p. Nair et al 5 confirmed the locus in the HLA region and presented two additional novel loci on chromosome 16q and 20p using 182 sib pairs in a genome-wide scan.…”