Association with Genetic Variants in the XXXX and NF-kB Pathways Discriminates between Mild and Severe Psoriasis Skin Disease.

@entity1 @entity2451 @entity1569 @entity14283 @entity23973 @entity32280 @entity15787 @entity18698 @entity18068 @entity4452
UNASSIGNED: Psoriasis is clinically heterogeneous, and symptoms can vary from mild almost cosmetic symptoms to severe disease requiring systemic therapy. Biomarkers predicting disease development are lacking. Herein we explored the genetic background in two polarized cohorts of carefully phenotyped @entity1 with long-term follow-up: consistent mild phenotype (n=696) and severe disease course requiring systemic therapy (n=715). All @entity1 were treated at the same dermatology department ensuring homogenous assessment. Genotyping included known @entity1569 -associated variants, with special focus on the @entity4452 and NF-kB pathways. A case-case study comparing severe and mild @entity1569 phenotypes, controlling for age at disease onset and gender, revealed significant differences between the two groups for SNPs in @entity14283 , @entity2451 , @entity15787 , @entity18068 , @entity23973 and @entity4452 . @entity18698 *06 associated equally in the mild and severe disease cohorts. Strong additive effects when combining @entity18698 *06 with @entity4452 , @entity14283 , @entity18068 , @entity2451 or @entity32280 were restricted to the severe cohort, indicating that activation of these pathways may influence disease severity in @entity1569 . No protective gene was identified in the mild cohort, suggesting that current screens have primarily identified @entity1569 variants associated with a more severe phenotype. These results demonstrate the importance of careful phenotyping and long-term clinical follow-up in genetic studies.
