ERAP1 molecular characterization: Identification of a de novo allelic variant

Padula, Maria Carmela; Leccese, Pietro; Padula, Angela; D’Angelo, Salvatore; Martelli, Giuseppe

doi:10.1111/tan.13262

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…ERAP1 encodes an amino-peptidase responsible for processing N-terminally extended antigenic precursors for optimal loading onto HLA molecules. The enzyme trimming efficiency has been related to the presence of SNPs influencing the dynamics of the open-closed conformational change (Kirino et al 2013;Conde-Jaldon et al 2014;Gul 2014Gul , 2015Ombrello et al 2015;Takeuchi et al 2015Takeuchi et al , 2016Wang et al 2017;Padula et al 2018Padula et al , 2019aPadula et al , 2019b.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, several BS susceptibility loci were highlighted outside the HLA in genome wide association studies (GWASs). Non-HLA variations have also been investigated and their association with BS has been demonstrated for several genes, such as Endoplasmic reticulum aminopeptidase 1 (ERAP1), Interleukin 10 (IL10), IL-23 receptor-IL-12 receptor β2 (IL23R-IL12RB2), Signal transducer and activator of transcription 4 (STAT4), C-C Motif Chemokine Receptor 1 (CCR1), Killer Cell Lectin Like Receptor C4 (KLRC4), Ubiquitin-associated domaincontaining protein 2 (UBAC2), Toll-like receptor 4 (TLR4), Mediterranean fever (MEFV), and Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) genes (Kirino et al 2013;Conde-Jaldon et al 2014;Gul 2014Gul , 2015Ombrello et al 2015;Sousa et al 2015;Takeuchi et al 2015Takeuchi et al , 2016Burillo-Sanz et al 2017;Jung et al 2017;Kang et al 2017;Wang et al 2017;Deng et al 2018;Padula et al 2018Padula et al , 2019aPadula et al , 2019b.…”

Section: Introductionmentioning

confidence: 99%

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A First Step for the Molecular Characterization of Neurological Involvement of Behçet Syndrome: an Italian Pivotal Study

Padula¹,

Leccese²,

Lascaro³

et al. 2020

J Mol Neurosci

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Behçet syndrome (BS) is a vasculitis characterized by several clinical manifestations including the rare neurological involvement (neuro-BS, NBS). The aim of our pivotal study was to investigate the mutational status of several inflammation-related genes in a cohort of Italian patients with and without the neurological involvement (20 NBS vs 40 no-NBS patients). The preliminary in silico single nucleotide polymorphism (SNP) selection and primer design were performed by NCBI Primer-Blast tool. Genomic DNA was isolated and amplified using PCR. PCR amplicons were sequenced and bioinformatically analysed. Twelve tagSNPs were selected and genotyped: ERAP1 rs30187, rs17482078, and rs27044; IL10 rs1800872 and rs1518111, IL12A rs17810546, IL23R rs17375018, IL23R-IL12RB2 rs924080, STAT4 rs7572482, CCR1 rs7616215, KLRC4 rs2617170, and UBAC2 rs3825427. ERAP1 and IL23R SNPs showed statistically significant higher frequencies in NBS group than no-NBS. ERAP1 rs30187 AA was more common in no-NBS patients (20.0% NBS vs 47.5% no-NBS; p < 0.05), while rs17482078 GA frequency was higher in NBS patients (55.0% NBS vs 22.5% no-NBS; p < 0.05, OR: 4.21). IL23R rs17375018 GG was more frequent in NBS group (65.0% NBS vs 40.0% no-NBS; p < 0.05), according to a previous finding. No other statistically significant differences were found. In conclusion, ERAP1 and IL23R SNPs were found associated with neurological involvement of BS. Additional and larger analyses were required to verify our preliminary findings.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A First Step for the Molecular Characterization of Neurological Involvement of Behçet Syndrome: an Italian Pivotal Study

Padula¹,

Leccese²,

Lascaro³

et al. 2020

J Mol Neurosci

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“…ERAP1 is characterized by several common polymorphisms encoding variant amino acids related not only to BD, but also to ankylosing spondylitis (AS) and psoriasis (47–51). The same SNPs associated to BD risk resulted protective against AS and psoriasis: this effect depends on the different HLA interacting with ERAP1 (46, 49). ERAP1 polymorphisms was a risk factor preferentially in BD patients with HLA-B * 51-positivity; ERAP1 rs17482078 (p.Arg725Gln) might influence the peptide repertoire binding to HLA-B * 51 (47).…”

Section: Geneticsmentioning

confidence: 96%

“…The gene encodes an amino-peptidase having the critical role to trim N-terminal of peptides. This mechanism was affected by the amino acids sequence of the corresponding protein (46–51). ERAP1 is characterized by several common polymorphisms encoding variant amino acids related not only to BD, but also to ankylosing spondylitis (AS) and psoriasis (47–51).…”

Section: Geneticsmentioning

confidence: 99%

Behçet’s Disease: An Overview of Etiopathogenesis

2019

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Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology hallmarked predominantly by mucocutaneous lesions and ocular involvement. BD shares some common features with autoimmune and autoinflammatory diseases and spondyloarthropathies (MHC-I-opathies). It is related to more than one pathogenic pathway triggered by environmental factors such as infectious agents in genetically predisposed subjects. The interplay between genetic background and immune system is linked to the BD presentation. Genetic factors have been investigated extensively, and several recent genome-wide association studies have confirmed HLA-B * 51 to be the strongest genetic susceptibility factor. However, new non-HLA susceptibility genes have been identified. Genetic variations in the genes encoding the cytokines could affect their function and be associated with disease susceptibility. Infectious agents such as Streptococcus sanguinis or the differences in salivary or gut microbiome composition can be considered to trigger the innate-derived inflammation, which is, subsequently, sustained by adaptive immune responses. Altered trimming of microbial and/or endogenous peptides by endoplasmic reticulum aminopeptidase 1 (ERAP1), presented by HLA-B * 51 , may play a key role in BD pathogenesis causing an alteration in T cell balance with downregulation of Tregs and expansion of Th1 and Th17. The activity of neutrophils is increased and there is an intense neutrophil infiltration in the early stage of inflammation in organs affected by the disease. Association with HLA-B * 51 and increased IL-17 response seems to have an important role in neutrophil activity. In this paper, we provide an overview of the most recent advances on BD etiopathogenesis.

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Genotyping of Italian patients with Behçet syndrome identified two novel ERAP1 polymorphisms using sequencing-based approach

et al. 2019

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ERAP1 molecular characterization: Identification of a de novo allelic variant

Abstract: The novel ERAP1 allelic variant is a missense polymorphism leading to the Arg53Pro substitution.

Cited by 5 publications

References 6 publications

A First Step for the Molecular Characterization of Neurological Involvement of Behçet Syndrome: an Italian Pivotal Study

A First Step for the Molecular Characterization of Neurological Involvement of Behçet Syndrome: an Italian Pivotal Study

Behçet’s Disease: An Overview of Etiopathogenesis

Genotyping of Italian patients with Behçet syndrome identified two novel ERAP1 polymorphisms using sequencing-based approach

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