PSORS7

PSORS7 (PSORS7 stands for Psoriasis Susceptibility 7) is a genetic locus on chromosome 1p. Psoriasis is one of the diseases associated with PSORS7.

Veal et al (2001) performed a genome-wide linkage analysis using 271 polymorphic markers in 284 sibling pairs from 158 independent families. They identified linkage at 6p21 (PSORS1) with a nonparametric linkage level (NPL) of 4.7 and at a new locus on 1p (NPL = 3.6) in all families studied. Markers at loci D1S197, D1S200, and D1S207 contributed to the NPL score of 3.6. Veal et al (2001) indicated that the EPS15 gene (600051), which encodes an intracellular substrate for the EGF receptor and is known to be overexpressed in psoriatic epidermis, lies within the critical region defined at 1p. Three other regions achieved NPL scores greater than 2.

Cargill et al. (2007) used 22 215 gene-centered SNPs in a case-control association study of psoriasis in three independent samples of white North American individuals and found a highly significant association with a SNP in the 3-prime UTR of the IL12B gene (161561) (reviewed in PSORS11; 612599). Because IL12B encodes the common IL12 p40 subunit of IL12 and IL23, Cargill et al (2007) individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines, IL12A (161560) and IL23A (605580), and their receptors: IL12RB1 (601604), IL12RB2 (601642), and IL23R (607562), which is located on chromosome 1p31.1. Haplotype analyses identified two IL23R missense SNPs that marked a common psoriasis-associated haplotype in all three studies. Individuals who were homozygous for both the IL12B and IL23R haplotypes had an increased risk of disease. These data and the previous observation that administration of an antibody specific for the IL12 p40 subunit to patients with psoriasis is highly effective (Kauffman et al. 2004) suggest that these genes play a fundamental role in the pathogenesis of psoriasis.

In a genome-wide association study of 1,359 psoriasis patients and 1,400 controls, Nair et al. (2009) found a significant association between psoriasis and rs2201841 in the IL23R gene (p = 3 x 10(-7)). The results were repeated in an additional 5,048 cases and 5,051 controls, yielding a combined p value of 3 x 10(-8). The G allele resulted in an odds ratio of 1.13.

Huffmeier et al. (2009) analyzed 4 variants in the IL12B and IL23R genes in 748 patients with psoriatic arthritis, 1,114 patients with psoriasis, and 937 controls. The strongest associations in both disease groups were found with IL12B variants rs3212227 and rs6887695 (p-values ranging from 2.10 x 10(-5) to 9.67 x 10(-7) with corresponding odds ratios of 1.43 to 1.50). The IL12B risk haplotype also showed an association in both groups (p-value on the order of 10(-6)). The effect for rs11209026 in the IL23R gene was slightly weaker in psoriasis (p = 2.42 x 10(-6)) and psoriatic arthritis (p = 0.002). The results confirmed previous studies that variants in the IL12B and IL23R genes are susceptibility factors for psoriasis and extended the findings to psoriatic arthritis.

1. Abbas Zadeh S et al. (2017) Phylogenetic profiling and gene expression studies implicate a primary role of PSORS1C2 in terminal differentiation of keratinocytes. Exp Dermatol 26:352-358.
2. Capon F et al (2007) Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum Genet 122: 201-206
3. Cargill M et al (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80: 273-390, 2007.
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