Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus

Eirís, Noemí; González-Lara, Leire; Santos‐Juanes, Jorge; Queiró, Rubén; Coto, Eliécer; Coto‐Segura, Pablo

doi:10.1016/j.jdermsci.2014.05.010

Cited by 76 publications

(53 citation statements)

References 30 publications

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“…Firstly, psoriasis and type 2 diabetes might share common genetic background. [28][29][30] Another explanation for insulin resistance in patients with psoriasis can be the presence of chronic inflammation. Psoriasis is characterized by a dysregulation of the innate immune system 31 and raised levels of cytokines play an essential role in the pathogenesis of not only psoriasis, but also in type 2 diabetes by promoting insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Patients with psoriasis are insulin resistant

Gyldenløve

Storgaard

Holst

et al. 2015

Journal of the American Academy of Dermatology

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Section: Discussionmentioning

confidence: 99%

Patients with psoriasis are insulin resistant

Gyldenløve

Storgaard

Holst

et al. 2015

Journal of the American Academy of Dermatology

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“…Several studies have previously highlighted the importance of genes and haplotypes in both the IL-23 as well as the NF-B pathways in psoriasis (Nair et al, 2009;Safrany et al, 2011;Safrany et al, 2013) as well as in many other immune-mediated diseases; PsA (Di Meglio et al, 2013;Eiris et al, 2014;Nair et al, 2010;Cargill et al, 2007;Franke et al, 2010;Strange et al, 2010;Bowes et al, 2011;Liu et al, 2008;Popa et al, 2013;Wang et al, 2012;Capon et al, 2007), Crohn's disease (Chua et al, 2012;Dinu et al, 2012;Jung et al, 2012), inflammatory bowel disease (Duerr et al, 2006;Safrany et al, 2013), ankylosing spondylitis (Safrany et al, 2009), celiac disease and multiple sclerosis (Nunez et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Association with Genetic Variants in the IL-23 and NF-κB Pathways Discriminates between Mild and Severe Psoriasis Skin Disease

Nikamo

Lysell

Ståhle

2015

Journal of Investigative Dermatology

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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 patients with long-term follow-up: consistent mild phenotype (n=696) and severe disease course requiring systemic therapy (n=715). All patients were treated at the same dermatology department ensuring homogenous assessment. Genotyping included known psoriasis-associated variants, with special focus on the IL-23 and NF-κB pathways. A case-case study comparing severe and mild psoriasis phenotypes, controlling for age at disease onset and gender, revealed significant differences between the two groups for SNPs in IL23R, NFKB1, IL21, IL12B, NFKBIL1 and IL23A. HLA-C*06 associated equally in the mild and severe disease cohorts. Strong additive effects when combining HLA-C*06 with IL23A, IL23R, IL12B, NFKB1 or TNIP1 were restricted to the severe cohort, indicating that activation of these pathways may influence disease severity in psoriasis. No protective gene was identified in the mild cohort, suggesting that current screens have primarily identified psoriasis variants associated with a more severe phenotype. These results demonstrate the importance of careful phenotyping and long-term clinical follow-up in genetic studies.

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“…Recently variants in some genes have been found to increase the risk for developing such other chronic diseases in patients with psoriasis. Variation at IL12B, IL23R, and IL23A would contribute not only to psoriasis susceptibility but also to risk of developing type 2 diabetes in the Caucasian population [28]. Genetic variants at CSMD1 were associated with cigarette smoking and those at TNIP1/ANXA6 were associated with alcohol use, affecting the risk for psoriasis, in the Han Chinese population [29].…”

Section: Genetic Background Of Psoriasismentioning

confidence: 99%