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Genetic variants of...
Genetic variants of the IL22 promoter associate to onset of psoriasis before puberty and increased IL-22 production in T cells.
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- Nikamo, Pernilla (författare)
- Karolinska Institutet
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- Cheuk, Stanley (författare)
- Karolinska Institutet
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- Lysell, Josefin (författare)
- Karolinska Institutet
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- Enerbäck, Charlotta (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet,Hudkliniken i Östergötland
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- Bergh, Kerstin (författare)
- Karolinska Institutet, Karolinska University Hospital, Stockholm
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- Xu Landén, Ning (författare)
- Karolinska Institutet
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- Eidsmo, Liv (författare)
- Karolinska Institutet
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- Ståhle, Mona (författare)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- Engelska.
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 134:6, s. 1535-1541
- Relaterad länk:
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http://www.jidonline...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Most psoriasis susceptibility genes were identified in cohorts of mixed clinical phenotypes and the exploration of genes in clinical subtypes is scarce. IL-22 has an established role in host defense and in psoriasis skin pathology, reflecting the delicate balance between control of infection and immunopathology. In a case-control study, we compared the genetic association to IL22 in psoriasis onset in patients between 0-9 (n=207), 10-20 (n=394), and 21-40 (n=468) years with healthy controls (n=1,529). Logistic regression analysis revealed association to regulatory elements in the IL22 promoter confined to onset of psoriasis before puberty (odds ratio=1.45, P<0.0007). The associated variants contain putative binding sites for AhR, a potent inducer of IL-22 expression. In a luciferase assay, transcriptional activity of a high-risk gene variant resulted in 80% higher promoter activity (P=0.012) compared with a low-risk variant. Ex vivo stimulated T cells from peripheral blood were analyzed with flow cytometry. Children with psoriasis carrying a high-risk variant produced 1.7 times more IL-22 compared with low-risk variants (P=0.042). Our combined genetic and functional data support the notion that a genetic IL22 variant that promotes epithelial barrier defense is preferentially enriched in and may precipitate the onset of psoriasis at an early age.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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