Genetic Study on Small Insertions and Deletions in Psoriasis Reveals a Role in Complex Human Diseases

Zhen, Qi; Yang, Zhenjun; Wang, Wenjun; Li, Bao; Bai, Mingzhou; Wu, Jing; Ge, Huiyao; Dong, Zirui; Shen, Juan; Tang, Huayang; Sun, Silong; Qiu, Ying; Xu, Jinjin; Qu, Xiaoxiao; Wang, Ying; Yi, Meihui; Hu, Huaqing; Xu, Yuanhong; Cheng, Hui; Liang, Bo; Gao, Jinping; Shao, Haojing; Jiang, Zhengwen; Gao, Qiang; Sun, Liangdan

doi:10.1016/j.jid.2019.03.1157

Cited by 25 publications

(16 citation statements)

References 58 publications

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“…At present, the relationship between ERAP1 and ERAP2 is not completely clear: there are suggestions that they can cooperate, but also that ERAP2 can regulate ERAP1 expression and activity ( 39 , 40 ), modifying the peptidome and, consequently, the expression of the HLA molecules in a subtype-dependent manner ( 23 ). LNPEP has been involved in diabetes ( 41 ) and associated with psoriasis ( 42 , 43 ), sharing the last feature with the other two aminopeptidases. Although not demonstrated in the literature, it is however still possible that LNPEP can contribute to disease pathogenesis by modulating the peptidome cross-presented by the HLA-I molecules ( 44 ).…”

Section: Disease Associationsmentioning

confidence: 99%

The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease

et al. 2020

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In the human genome, the aminopeptidases ERAP1, ERAP2 and LNPEP lie contiguously on chromosome 5. They share sequence homology, functions and associations with immune-mediated diseases. By analyzing their multifaceted activities as well as their expression in the zoological scale, we suggest here that the progenitor of the three aminopeptidases might be LNPEP from which the other two aminopeptidases could have derived by gene duplications. We also propose that their functions are partially redundant. More precisely, the evolutionary story of the three aminopeptidases might have been dictated by their role in regulating the renin–angiotensin system, which requires their controlled and coordinated expression. This hypothesis is supported by the many species that lack one or the other gene as well as by the lack of ERAP2 in rodents and a null expression in 25% of humans. Finally, we speculate that their role in antigen presentation has been acquired later on during evolution. They have therefore been diversified between those residing in the ER, ERAP1 and ERAP2, whose role is to refine the MHC-I peptidomes, and LNPEP, mostly present in the endosomal vesicles where it can contribute to antigen cross-presentation or move to the cell membrane as receptor for angiotensin IV. Their association with autoinflammatory/autoimmune diseases can therefore be two-fold: as “contributors” to the shaping of the immune-peptidomes as well as to the regulation of the vascular response.

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Section: Disease Associationsmentioning

confidence: 99%

The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease

et al. 2020

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“…Studies on CCNB1, RRM2 have been reported in AD [51,52] . And CCNB1, KIF20A, NCAPG, MKI67, NUF2, RRM2, TTK, and UBE2C are all closely linked with psoriasis [51,[53][54][55][56][57] . For the rst time, our study identi ed that hub genes CDC20, KIF20A, NCAPG, TK1, TTK, UBE2C, CEP55, MELK, MKI67, NUF2, UHRF1 may become novel diagnostic biomarker in AD, and hub genes CDC20, CEP55, MELK, TK1, UHRF1 are predictors of psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-based Exploration of the Molecular Mechanism of Autophagy-related Differentially Expressed Genes in Psoriasis and Atopic Dermatitis

Yang

Zhu

Dang

et al. 2022

Preprint

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Atopic dermatitis (AD) and psoriasis are both chronic recurrent inflammatory skin diseases. However, research on AD and psoriasis co-morbidity is still in early stages and limited to clinical manifestations. In this study, we studied the role of autophagy-related genes in AD and psoriasis by used integrated bioinformatics methods. We obtained differentially expressed genes (DEGs) for psoriasis and AD by analyzing the datasets GSE14905(psoriasis) and GSE32924(atopic dermatitis). We further identified autophagy-related DEGs by intersecting above-obtained DEGs with autophagy-related genes. Then we performed Gene Ontology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). And hub genes were identified by constructing protein-protein interaction (PPI) networks. Finally, we conducted ROC validation of hub genes and explored the correlation of hub genes with other molecules and immune cells in atopic dermatitis and psoriasis. Finally, we concluded that the 13 autophagy-related genes are involved in the pathogenesis and progression of AD and psoriasis by regulating cell cycle, cellular components eradication and drug metabolisms, and could predict the onset and severity of diseases.

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“…The data set we used in this paper was initiated as independent second-stage validation of 1326 genes after first-stage GWAS discoveries of psoriasis-related loci (Tang et al 2014). A total of 21,309 samples were collected through collaborations with multiple Chinese hospitals (Sheng et al 2014;Tang et al 2014;Zhou et al 2016;Zhen et al 2019). All individuals are of Han Chinese ancestry.…”

Section: Study Sample and Targeted Resequencingmentioning

confidence: 99%

Deep sequencing of 1320 genes reveals the landscape of protein-truncating variants and their contribution to psoriasis in 19,973 Chinese individuals

Zhen

Bai

et al. 2021

Genome Res.

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Protein-truncating variants (PTVs) have important impacts on phenotype diversity and disease. However, their population genetics characteristics in more globally diverse populations are not well defined. Here, we describe patterns of PTVs in 1320 genes sequenced in 10,539 healthy controls and 9434 patients with psoriasis, all of Han Chinese ancestry. We identify 8720 PTVs, of which 77% are novel, and estimate 88% of all PTVs are deleterious and subject to purifying selection. Furthermore, we show that individuals with psoriasis have a significantly higher burden of PTVs compared to controls (P = 0.02). Finally, we identified 18 PTVs in 14 genes with unusually high levels of population differentiation, consistent with the action of local adaptation. Our study provides insights into patterns and consequences of PTVs.

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Genetic Study on Small Insertions and Deletions in Psoriasis Reveals a Role in Complex Human Diseases

Cited by 25 publications

References 58 publications

The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease

The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease

Bioinformatics-based Exploration of the Molecular Mechanism of Autophagy-related Differentially Expressed Genes in Psoriasis and Atopic Dermatitis

Deep sequencing of 1320 genes reveals the landscape of protein-truncating variants and their contribution to psoriasis in 19,973 Chinese individuals

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