PSORS4

PSORS4 (Psoriasis Susceptibility 4) is a genetic locus on chromosome 1q21. Diseases associated with PSORS4 include psoriasis.

Capon et al (2001) performed linkage disequilibrium analysis to achieve a more precise localization of PSORS4. Since psoriasis is considered a polygenic disease, the authors examined the relationship between the HLA-C (142840) and 1q21 loci in terms of their contribution to psoriasis susceptibility. They demonstrated an association with HLA-Cw6. In the second phase of the study, Capon et al. (1999) subjected fifteen 1q-linked families to an analysis of the correlation between nonparametric linkage scores in HLA-C and D1S305. The data could be interpreted as preliminary evidence for an epistatic interaction between the psoriasis susceptibility loci 1q21 and 6p21(PSORS1).

Zenz et al. (2005) reported that epidermal keratinocytes in psoriatic lesions have decreased expression of JunB (165161), a gene localized to the psoriasis susceptibility region PSORS6 (605364).

In a genome-wide association study of 1 139 patients with psoriasis and 1 132 controls of Chinese Han ancestry, Zhang et al. (2009) found an association between psoriasis and rs4085613 within the LCE gene cluster on chromosome 1q21. The results were replicated in two independent samples of 5,182 cases and 6,516 controls of Chinese Han ancestry and 539 cases and 824 controls of Chinese Uygur ancestry, respectively, yielding a combined p-value of 6.69 x 10(-30).

In a genome-wide search for copy number variants (CNVs) using a sample pooling approach, de Cid et al. (2009) found that a deletion encompassing the LCE3B (612614) and LCE3C (612615) genes on chromosome 1q21 was significantly associated with psoriasis in a total of 557 samples from Spain. The results were replicated in four additional cohorts from the Netherlands, Italy, and the United States, yielding a total of 2,831 cases and a combined p-value of 1.38 x 10(-8). The LCE3C-LEC3B deletion showed epistatic effects with the HLA-Cw6 allele on the development of psoriasis in Dutch samples and multiplicative effects in the other samples. RT-PCR studies indicated that LCE expression in normal human epidermis can be induced by skin barrier dysfunction and is highly expressed in psoriatic lesions, suggesting that impaired skin barrier function may play a role in psoriasis susceptibility.

1. Capon F et al. (1999) Searching for psoriasis susceptibility genes in Italy: genome scan and evidence for a new locus on chromosome 1. J Invest Derm 112: 32-35.
2. Capon F et al. (2001) Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21. J Invest Derm 116: 728-730.
3. Chen H et al. (2009) Association of skin barrier genes within the PSORS4 locus is enriched in Singaporean Chinese with early-onset psoriasis. J Invest Derm 129: 606-614
4. De Cid R et al (2009) Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nature Genet 41: 211-215.
5. Giardina, E., Capon, F., De Rosa, M. C., Mango, R., Zambruno, G., Orecchia, A., Chimenti, S., Giardina, B., Novelli, G. Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus. Ann. Hum. Genet. 68: 639-645, 2004. [PubMed: 15598222, related citations] [Full Text]
6. Giardina, E., Sinibaldi, C., Chini, L., Moschese, V., Marulli, G., Provini, A., Rossi, P., Paradisi, M., Chimenti, S., Galli, E., Brunetti, E., Girolomoni, G., Novelli, G. Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic dermatitis (ATOD2) on human chromosome 1q21. Hum. Hered. 61: 229-236, 2006. [PubMed: 16912508, related citations] [Full Text]
7. Zenz R et al (2006) Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 437: 369-375.
8. Zhang X-J et al. (2009) Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nature Genet 41: 205-210.