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与银屑病及银屑病患者发生银屑病关节炎相关的基因多态性。

Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis.

作者信息

Loft Nikolai Dyrberg, Skov Lone, Rasmussen Mads Kirchheiner, Gniadecki Robert, Dam Tomas Norman, Brandslund Ivan, Hoffmann Hans Jürgen, Andersen Malene Rohr, Dessau Ram Benny, Bergmann Ann Christina, Andersen Niels Møller, Abildtoft Mikkel Kramme, Andersen Paal Skytt, Hetland Merete Lund, Glintborg Bente, Bank Steffen, Vogel Ulla, Andersen Vibeke

机构信息

Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

出版信息

PLoS One. 2018 Feb 1;13(2):e0192010. doi: 10.1371/journal.pone.0192010. eCollection 2018.

Abstract

BACKGROUND

Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables.

METHODS

Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO.

RESULTS

Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO.

CONCLUSION

Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.

摘要

背景

银屑病(PsO)是一种主要表现为皮肤症状的慢性炎症性疾病。约三分之一的银屑病患者会发展为银屑病关节炎(PsA),其余患者则仅有皮肤型银屑病(PsC)。这两种表型具有共同的免疫学特征,但遗传因素不同,这可能部分由基因变量来解释。

方法

采用候选基因方法,我们研究了37个调节炎症的基因中的53个单核苷酸多态性(SNP)。我们总共评估了来自DERMBIO的480例银屑病患者,其中151例患有10年或更长时间的皮肤型银屑病(PsC10),来自DANBIO的459例银屑病关节炎患者,以及795名健康对照。使用逻辑回归分析,对年龄和性别进行粗校正和调整后,我们评估了基因变异与银屑病、PsC10和银屑病关节炎之间的关联,以及基因变异与银屑病患者中银屑病关节炎发生之间的关联。

结果

10个基因中的11个多态性与银屑病和/或PsC和/或银屑病关节炎存在名义上的关联(P < 0.05)。在以5%的错误发现率进行多重检验校正后,两个SNP仍然显著:TNF(rs361525)与银屑病、PsC10和银屑病关节炎相关;IL12B(rs6887695)与银屑病相关。

结论

在一组丹麦中重度银屑病患者中,IL12B和TNF基因中的两个SNP与银屑病易感性相关。没有一个SNP与单纯皮肤型银屑病或银屑病关节炎有特异性关联。

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