HLA-C*06:02-independent, gender-related association of PSORS1C3 and PSORS1C1/CDSN single-nucleotide polymorphisms with risk and severity of psoriasis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-08

AUTHORS

Andrzej Wiśniewski, Łukasz Matusiak, Aneta Szczerkowska-Dobosz, Izabela Nowak, Piotr Kuśnierczyk

ABSTRACT

Psoriasis vulgaris (PsV) is a common, chronic skin disease with a complex genetic and environmental etiology. We investigated, in 461 psoriatic patients and 454 healthy controls, the associations with psoriasis of four single-nucleotide polymorphisms (SNPs) from the psoriasis susceptibility 1 (PSORS1) interval: rs1062470 (PSORS1C1/CDSN), rs887466 (PSORS1C3), rs2894207 and rs10484554 (LOC105375015). The minor alleles of three SNPs (rs1062470A, rs2894207C and rs10484554T) strongly increased the disease risk (OR = 2.17, p < 0.0001; OR = 2.33, p < 0.0001 and OR = 2.68, p < 0.0001, respectively), whereas the minor A allele of rs887466 exerted a protective effect (OR = 0.73, p = 0.001). The strength of association for SNPs was the highest in patients with very early onset psoriasis (≤ 20 years), while in late onset psoriasis (> 40 years) the association was the weakest. The haplotype rs1062470A/rs887466G/rs2894207C/rs10484554T highly significantly increased the disease risk (OR = 3.58, p = 8.0e-027), while the haplotypes rs1062470G/rs887466A/rs2894207T/rs10484554C and rs1062470G/rs887466G/rs2894207T/rs10484554C were strongly protective (OR = 0.65, p = 0.002 and OR = 0.55, p = 2.4e-009, respectively). Additionally, we showed a HLA-C*06:02-independent gender-related effect of the rs887466A allele which was protective against psoriasis in males (OR = 0.61, p = 9.2e-005), but not in females (p = 0.66). We also demonstrated a correlation of PASI score value with rs1062470 genotype, and again only in male patients (p = 0.006) and HLA-C*06:02-independent. Our results show, for the first time, the male-only associations of the PSORS1C3 gene with psoriasis risk and of the PSORS1C1/CDSN gene with severity of disease. However, the age dependent associations need to be validated in larger sample sizes as well as in other populations. More... »

PAGES

957-966

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00438-018-1435-4

DOI

http://dx.doi.org/10.1007/s00438-018-1435-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101785769

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29589160


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