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TNFαIP3 和 IL12B 基因多态性与埃及队列寻常型银屑病的相关性。

TNFAIP3 and IL12B gene polymorphisms associated with psoriasis vulgaris in an Egyptian cohort.

机构信息

Department of Dermatology, University of Lübeck, Lübeck, Germany.

Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.

出版信息

J Eur Acad Dermatol Venereol. 2015 Jul;29(7):1297-301. doi: 10.1111/jdv.12799. Epub 2014 Nov 18.

Abstract

BACKGROUND

Psoriasis vulgaris is a common chronic inflammatory skin disease. Development of early onset psoriasis is, to some extent, genetically determined and a strong association with the major histocompatibility complex HLA-Cw6 has been demonstrated. The use of genome-wide association studies has highlighted novel genes associated with the development of psoriasis as IL12B, IL23R, TNFAIP3 and IL13 for instance. The majority of these studies were performed on cohorts of European descent.

OBJECTIVE

To determine whether inter-ethnic differences exist in the genetic susceptibility to psoriasis, we genotyped single-nucleotide polymorphism variations in the vicinity of candidate genes in 132 Egyptian patients and 175 healthy controls.

METHODS

Blood samples of patients and controls were screened for nucleotide polymorphisms in four candidate genes by TaqMan single-nucleotide polymorphisms Genotyping Assays.

RESULTS

We found a significant association between psoriasis and the single-nucleotide polymorphism rs610604, within the TNFAIP3 gene. The TNFAIP3 gene is involved in the TNF-α signalling cascade (P-value: 0.004952), a key step in the pathogenesis of psoriasis. Although there was no significant association found between rs610604 (IL12B) and rs11209026 (IL23R) in this population, the interaction of these two genes showed a significant association with psoriasis (P-value: 0.025). Moreover, when selecting the patients with early disease onset (less than 30 years), we also found that the association of IL12B and psoriasis was highly significant (P-value 1.14 × 10(-12)). No association between rs20541 (IL13) and psoriasis was observed in our Egyptian cohort.

CONCLUSION

Replicating the association of single-nucleotide polymorphisms in the TNFAIP3, IL12B and IL23R genes with psoriasis vulgaris, in subjects from different ethnic backgrounds, underlines their importance in the pathogenesis of the disease. In contrast, the lack of any association between rs20541 (IL13) and psoriasis in our Egyptian cohort suggests the existence of important inter-ethnic genetic differences in psoriasis susceptibility.

摘要

背景

寻常型银屑病是一种常见的慢性炎症性皮肤病。银屑病的早期发病在一定程度上是由遗传决定的,并且已经证实与主要组织相容性复合体 HLA-Cw6 强相关。全基因组关联研究已经突出了与银屑病发展相关的新基因,例如 IL12B、IL23R、TNFAIP3 和 IL13 等。这些研究大多数是在欧洲血统的队列中进行的。

目的

为了确定银屑病的遗传易感性是否存在种族间差异,我们对 132 名埃及患者和 175 名健康对照者候选基因附近的单核苷酸多态性进行了基因分型。

方法

通过 TaqMan 单核苷酸多态性基因分型检测,对患者和对照者的血液样本进行候选基因中的核苷酸多态性筛查。

结果

我们发现 TNFAIP3 基因内的单核苷酸多态性 rs610604 与银屑病显著相关。TNFAIP3 基因参与 TNF-α 信号通路(P 值:0.004952),这是银屑病发病机制中的关键步骤。虽然在该人群中未发现 rs610604(IL12B)和 rs11209026(IL23R)之间存在显著关联,但这两个基因的相互作用与银屑病显著相关(P 值:0.025)。此外,当选择发病年龄较早(<30 岁)的患者时,我们还发现 IL12B 与银屑病的关联具有高度显著性(P 值:1.14×10(-12))。在我们的埃及队列中,未观察到 rs20541(IL13)与银屑病之间存在关联。

结论

在不同种族背景的受试者中复制 TNFAIP3、IL12B 和 IL23R 基因中单核苷酸多态性与寻常型银屑病的关联,强调了它们在疾病发病机制中的重要性。相比之下,在我们的埃及队列中,rs20541(IL13)与银屑病之间缺乏任何关联表明,银屑病易感性存在重要的种族间遗传差异。

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