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Polymorphisms in IL36G gene are associated with plaque psoriasis

BACKGROUND: Plaque psoriasis is a non-contagious skin disease in which characteristic red and flaky lesions result from a dysregulation involving both innate and adaptive immune mechanisms. Several cytokines have been implicated in these processes and lately interleukin (IL)-36 family members have b...

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Autores principales: Traks, Tanel, Keermann, Maris, Prans, Ele, Karelson, Maire, Loite, Ulvi, Kõks, Gea, Silm, Helgi, Kõks, Sulev, Kingo, Külli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330488/
https://www.ncbi.nlm.nih.gov/pubmed/30634937
http://dx.doi.org/10.1186/s12881-018-0742-2
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author Traks, Tanel
Keermann, Maris
Prans, Ele
Karelson, Maire
Loite, Ulvi
Kõks, Gea
Silm, Helgi
Kõks, Sulev
Kingo, Külli
author_facet Traks, Tanel
Keermann, Maris
Prans, Ele
Karelson, Maire
Loite, Ulvi
Kõks, Gea
Silm, Helgi
Kõks, Sulev
Kingo, Külli
author_sort Traks, Tanel
collection PubMed
description BACKGROUND: Plaque psoriasis is a non-contagious skin disease in which characteristic red and flaky lesions result from a dysregulation involving both innate and adaptive immune mechanisms. Several cytokines have been implicated in these processes and lately interleukin (IL)-36 family members have become more recognised among them. Thus far, genetic studies have only investigated IL36RN gene of this family in relation to pustular psoriasis. Since IL36G has previously demonstrated markedly increased levels in plaque psoriasis patients and is linked to IL-23/IL-17 axis critical in psoriasis pathology, it was chosen to be the focus of current report. METHODS: Eleven SNPs from IL36G region were genotyped in 728 plaque psoriasis patients and 320 healthy control individuals. Allele and haplotype frequencies between patients and controls were assessed by respective association tests. For more specific analyses, the patients were assigned into subgroups according to sex, age of disease onset, occurrence of psoriasis among relatives, seasonal aggravation, arthritis symptoms, body surface area (BSA) scores, and Psoriasis Area and Severity Index (PASI) scores. RESULTS: The most significant results were obtained with SNPs rs28947206, rs28947207 and rs28947211 that were associated in entire plaque psoriasis analysis (multiple testing adjusted p value (p(adj)) = 0.0054, p(adj) = 0.0017 and p(adj) = 0.0001) and also several subgroups. The first two of those SNPs were included in the same haplotype block with rs28947205 and rs12328178, and two of the respective haplotypes, CAGC and TGTT, provided similarly significant associations (p(adj) = 0.0462 and p(adj) = 0.0047). CONCLUSIONS: The associated SNPs of this study or those in linkage disequilibrium with them could potentially affect the functionality of IL-36γ cytokine, which in turn may impact plaque psoriasis pathology. For instance, these variants could influence IL-36γ expression or 3D structure, thereby altering its ability to induce chemokine production in keratinocytes and various immune cells. The precise mechanisms of these actions are currently unknown and out of the scope of this study. To conclude, the present genetic association results confirm the proposed role of IL-36γ in plaque psoriasis development, with corresponding causal effects to be determined in forthcoming research.
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spelling pubmed-63304882019-01-16 Polymorphisms in IL36G gene are associated with plaque psoriasis Traks, Tanel Keermann, Maris Prans, Ele Karelson, Maire Loite, Ulvi Kõks, Gea Silm, Helgi Kõks, Sulev Kingo, Külli BMC Med Genet Research Article BACKGROUND: Plaque psoriasis is a non-contagious skin disease in which characteristic red and flaky lesions result from a dysregulation involving both innate and adaptive immune mechanisms. Several cytokines have been implicated in these processes and lately interleukin (IL)-36 family members have become more recognised among them. Thus far, genetic studies have only investigated IL36RN gene of this family in relation to pustular psoriasis. Since IL36G has previously demonstrated markedly increased levels in plaque psoriasis patients and is linked to IL-23/IL-17 axis critical in psoriasis pathology, it was chosen to be the focus of current report. METHODS: Eleven SNPs from IL36G region were genotyped in 728 plaque psoriasis patients and 320 healthy control individuals. Allele and haplotype frequencies between patients and controls were assessed by respective association tests. For more specific analyses, the patients were assigned into subgroups according to sex, age of disease onset, occurrence of psoriasis among relatives, seasonal aggravation, arthritis symptoms, body surface area (BSA) scores, and Psoriasis Area and Severity Index (PASI) scores. RESULTS: The most significant results were obtained with SNPs rs28947206, rs28947207 and rs28947211 that were associated in entire plaque psoriasis analysis (multiple testing adjusted p value (p(adj)) = 0.0054, p(adj) = 0.0017 and p(adj) = 0.0001) and also several subgroups. The first two of those SNPs were included in the same haplotype block with rs28947205 and rs12328178, and two of the respective haplotypes, CAGC and TGTT, provided similarly significant associations (p(adj) = 0.0462 and p(adj) = 0.0047). CONCLUSIONS: The associated SNPs of this study or those in linkage disequilibrium with them could potentially affect the functionality of IL-36γ cytokine, which in turn may impact plaque psoriasis pathology. For instance, these variants could influence IL-36γ expression or 3D structure, thereby altering its ability to induce chemokine production in keratinocytes and various immune cells. The precise mechanisms of these actions are currently unknown and out of the scope of this study. To conclude, the present genetic association results confirm the proposed role of IL-36γ in plaque psoriasis development, with corresponding causal effects to be determined in forthcoming research. BioMed Central 2019-01-11 /pmc/articles/PMC6330488/ /pubmed/30634937 http://dx.doi.org/10.1186/s12881-018-0742-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Traks, Tanel
Keermann, Maris
Prans, Ele
Karelson, Maire
Loite, Ulvi
Kõks, Gea
Silm, Helgi
Kõks, Sulev
Kingo, Külli
Polymorphisms in IL36G gene are associated with plaque psoriasis
title Polymorphisms in IL36G gene are associated with plaque psoriasis
title_full Polymorphisms in IL36G gene are associated with plaque psoriasis
title_fullStr Polymorphisms in IL36G gene are associated with plaque psoriasis
title_full_unstemmed Polymorphisms in IL36G gene are associated with plaque psoriasis
title_short Polymorphisms in IL36G gene are associated with plaque psoriasis
title_sort polymorphisms in il36g gene are associated with plaque psoriasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330488/
https://www.ncbi.nlm.nih.gov/pubmed/30634937
http://dx.doi.org/10.1186/s12881-018-0742-2
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