<scp>TNFAIP</scp>3 and <scp>IL</scp>12B gene polymorphisms associated with psoriasis vulgaris in an Egyptian cohort

Haase, Ozan; Mosaad, Heba; El-Darouti, Mohammad Ali; El-Ramly, Amany Z.; Samir, N.; Abdelhady, Mohamed; Samir, Mai; Elgharib, Ibrahim; Salah, S.; el-Shennawy, F; Mosaad, Youssef M.; Elwan, Nadia; Salem, Hatem A.; Abdelgaber, Soheir; Recke, Andreas; Möller, Steffen; Zillikens, Detlef; Ibrahim, Saleh M.

doi:10.1111/jdv.12799

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…In our study, no signal was detected within the IL23R and IL12B genes as it was published in previous findings by Haase et al . This can be explained that the statistical power in our study estimates variant with odds ratio of 2 or more with a 80% probability; however, the odds ratio of the non‐replicated finding is lower justifying why they did not achieve significance such as IL23R variant rs9988642 that has an odds ratio of 1.4 .…”

Section: Resultssupporting

confidence: 58%

“…To date, there has been no published GWAS or sequencing‐based association studies on the Egyptian population apart from an association study of four SNPs (rs610604 [ TNFAIP3 ], rs3212227 [ IL12B ], rs11209026 [ IL23R ] and rs20541 [ IL13 ]) with psoriasis performed on a cohort of restricted sample size . The aim of this study was to perform the first comprehensive GWAS in an Egyptian population, identifying population specific psoriasis susceptibility loci.…”

Section: Questions Addressedmentioning

confidence: 99%

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Genome‐wide association study of psoriasis in an Egyptian population

Bejaoui

Witte

Abdelhady

et al. 2019

Experimental Dermatology

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Psoriasis is a chronic inflammatory disorder of the skin, with genetic factors reportedly involved in the disease pathogenesis. Numerous studies reported psoriasis candidate genes. However, these tend to involve mostly in the European and Asian populations. Here, we report the first genome‐wide association study (GWAS) in an Egyptian population, identifying susceptibility variants for psoriasis using a two‐stage case‐control design. In the first discovery stage, we carried out a genome‐wide association analysis using the Infinium® Global Screening Array‐24 v1.0, on 253 cases and 449 control samples of Egyptian descent. In the second replication stage, 26 single‐nucleotide polymorphisms (SNPs) were selected for replication in additional 321 cases and 253 controls. In concordance with the findings from previous studies on other populations, we found a genome‐wide significant association between the MHC locus and the disease at rs12199223 (Pcomb = 6.57 × 10−18) and rs1265181 (Pcomb = 1.03 × 10−10). Additionally, we identified a novel significant association with the disease at locus, 4q32.1 (rs12650590, Pcomb = 4.49 × 10−08) in the vicinity of gene GUCY1A3, and multiple suggestive associations, for example rs10832027 (Pcomb = 7.28 × 10−06) and rs3770019 (Pcomb = 1.02 × 10−05). This proposes the existence of important interethnic genetic differences in psoriasis susceptibility. Further studies are necessary to elucidate the downstream pathways of the new candidate loci.

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Section: Resultssupporting

confidence: 58%

Section: Questions Addressedmentioning

confidence: 99%

Genome‐wide association study of psoriasis in an Egyptian population

Bejaoui

Witte

Abdelhady

et al. 2019

Experimental Dermatology

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“…Keratinocyte-specific deletion of A20 results in epidermal hyperproliferation and ectodermal defects, but skin infiltration of immune cells has not been observed (Lippens et al, 2011). Genome-wide association studies identified TNFAIP3/A20 as a susceptibility locus for psoriasis (Haase et al, 2015;Indhumathi et al, 2015;Li et al, 2014;Nair et al, 2009;and Zhang et al, 2015), and its role as a negative regulator in Th2-associated lung inflammation, in particular through its expression by dendritic cells, has been well characterized (Schuijs et al, 2015;Vroman et al, 2018). On the other hand, some cases of A20 haploinsufficiency yield distinct autoinflammatory and/or autoimmune skin pathology, possibly with skin ulcerations and pustular abscesses (Kadowaki et al, 2017;Takagi et al, 2017;Zhou et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with Atopic Dermatitis and Psoriasis

Devos

Mogilenko

Fleury

et al. 2019

Journal of Investigative Dermatology

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Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 is down-regulated in involved epidermis, but not in dermis, of psoriasis and atopic dermatitis patients, suggesting that loss of A20 expression in keratinocytes increases the vulnerability for psoriasis/atopic dermatitis induction. We have previously shown that epidermis-specific A20 knockout mice (A20) develop mild epidermal hyperplasia but no macroscopic skin inflammation. We now show that various cytokines and chemokines are up-regulated in A20 mouse skin. A20 mice also display systemic proinflammatory changes, even in the absence of skin immune cell infiltration, and an exacerbated disease severity upon induction of experimental psoriasis, atopic dermatitis, or skin barrier disruption. Keratinocytes showed increased proinflammatory gene expression in the absence of A20 in unstimulated and IL-17A-stimulated conditions, in part resulting from uncontrolled MyD88-dependent signaling. Our findings indicate that absence of A20 in keratinocytes leads to systemic inflammation at homeostatic conditions and is sufficient to exacerbate inflammatory skin disorders associated with different immune profiles by increasing cytokine and chemokine expression.

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“…Of the 13 articles, 11 articles containing original data for rs610604. These studies were performed in UK [19], Egypt [20], India [21], China [22][23][24][25], Pakistani [26], USA [27], Sweden [28], México [29]. In all, these studies included 11,556 psoriasis patients and 16,720 controls.…”

Section: Study Characteristicsmentioning

confidence: 99%

Association of rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms with psoriasis susceptibility: a meta-analysis of case-control studies

Gong

Gao

et al. 2020

BMC Med Genet

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Background: To date, the fundamental pathophysiology underlying the occurrence and progression of psoriasis are still unanswered questions. Genome-wide association surveys have revealed that TNFAIP3 and TNIP1 were key biomarkers for psoriasis. Here, we intended to conduct a survey on the association between TNFAIP3 and TNIP1 gene polymorphisms and psoriasis risk. Methods: A comprehensive search of four online databases-China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Cochrane Library was undertaken up to August 25, 2019. We chose allele genetic model to deal with the original data. Newcastle-Ottawa scale (NOS) was used to evaluate the risk bias of each study. The RevMan 5.3 software was used to calculate the combined odds ratio and 95% confidence interval. Results: In total, we included 13 case-control studies consist of 13,908 psoriasis patients and 20,051 controls in this work. Our results demonstrated that rs610604 in TNFAIP3 polymorphism was significantly associated with psoriasis risk using random-effect model (G vs. T, OR = 1.19, 95% CI: 1.09-1.31, P = 0.0002), and a significant association between rs17728338 in TNIP1 polymorphism and psoriasis vulnerability using fixed-effect model (A vs. G, OR = 1.69, 95% CI:1.58-1.80, P < 0.00001). Conclusions: Our findings indicated that rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms were associated with psoriasis susceptibility.

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

Cited by 11 publications

References 23 publications

Genome‐wide association study of psoriasis in an Egyptian population

Genome‐wide association study of psoriasis in an Egyptian population

Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with Atopic Dermatitis and Psoriasis

Association of rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms with psoriasis susceptibility: a meta-analysis of case-control studies

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