Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression

Burkhardt, Jana; Blume, Mechthild; Petit-Teixeira, Élisabeth; Teixeira, Vítor Hugo; Steiner, Anke; Quente, Elfi; Wolfram, Grit; Scholz, Markus; Pierlot, Céline; Migliorini, Paola; Bombardieri, Stefano; Balsa, Alejandro; Westhovens, René; Barrera, Pilar; Radstake, Timothy R. D. J.; Alves, Helena; Bardin, Thomas; Prum, Bernard; Emmrich, Frank; Cornélis, François; Ahnert, Peter; Kirsten, Holger

doi:10.1371/journal.pone.0103872

Cited by 23 publications

(20 citation statements)

References 64 publications

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“…ERAP1 is an aminopeptidase involved in trimming HLA class I-binding precursors and related with ankylosing spondylitis [21] , LNPEP is a zinc-dependent aminopeptidase that cleaves peptide hormones such as GLUT4 (a glucose transporter involved in diabetes mellitus), but also interacts with MHC class I molecules [22] , and CAST is an endogenous calpain inhibitor related with rheumatic disease [23] . LRP4 is related to syndactyly and hyperostosis [24] and RIOK2 is associated with a rare form of congenital anaemia [25] .…”

Section: Resultsmentioning

confidence: 99%

Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar

et al. 2015

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Objective: The aim of this study is to evaluate the fraction of putatively deleterious variants within genomic runs of homozygosity (ROH) regions in an inbred and selected cohort of Qatari individuals. Methods: High-density SNP array analysis was performed in 36 individuals, and for 14 of them whole-exome sequencing (WES) was also carried out. Results: In all individuals, regions characterized by a high (hotspot) or low (coldspot) degree of homozygosity in all the analysed individuals were mapped, and the most frequent hotspot regions were selected. WES data were exploited to identify the single nucleotide variations (SNVs) harboured by genes located within both regions in each individual. Evolutionary conservation-based algorithms were employed to predict the potential deleteriousness of SNVs. The amount of in silico predicted deleterious SNVs was significantly different (p < 0.05) between homozygosity hotspot and coldspot regions. Conclusion: Genes located within ROH hotspot regions contain a significant burden of predicted putatively deleterious variants compared to genes located outside these regions, suggesting inbreeding as a possible mechanism allowing an enrichment of putatively deleterious variants at the homozygous state.

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Section: Resultsmentioning

confidence: 99%

Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar

et al. 2015

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“…10 More importantly, the citrullinated molecules, the indicator of inflammation process, are no longer the unique event in RA and can also be detected in patients with OA. 18 Although we know the similarities and differences between OA and RA, what specific roles FLSs playing in the mechanisms of OA and RA are still unclear. 13 These similar pathological features can explain some similar clinical symptoms and imaging results in OA and RA patients.…”

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confidence: 99%

Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA) based on microarray profiles of human joint fibroblast‐like synoviocytes

Cai

Jiang

et al. 2018

Cell Biochemistry & Function

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The purpose of the present study was to investigate the underlying molecular mechanism of osteoarthritis (OA) and rheumatoid arthritis (RA) based on microarray profiles. Three human joint fibroblast-like synoviocytes (FLSs) microarray profiles including 26 OA samples, 33 RA samples, and 20 healthy control (HC) samples were downloaded from the GEO database. Differentially expressed genes (DEGs) between OA and HC (DEGsOA) and RA and HC (DEGsRA) were identified. Co-expressed and specific genes were analysed between DEGsOA and DEGsRA. Gene ontology, KEGG pathway enrichment, PPI network, and GSEA were performed to predict the function of DEGs. Two hundred seventy-six and 410 differential genes in DEGsOA and DEGsRA were observed. One hundred fifty coexpressed genes and 126 OA-specific genes (SELE, SERPINE1, and NFKBIA were the key genes) between DEGsOA and DEGsRA were enriched in the tumour necrosis factor (TNF) signalling pathway. However, 260 RA-specific genes of which the key genes were CCR5, CCR7, CXCR4, CCL5, and CCR4 were enriched in chemokine signalling pathway. Therefore, FLSs might exert an inflammatory effect by regulating TNF signalling pathway, targeting SELE, SERPINE1, and NFKBIA during the process of OA. Although TNF signalling pathway was also involved in the synovitis of RA, chemokine signalling pathway played the key role in RA FLSs mediating cell migration, invasion, and release of chemotaxis. In addition, CCR5, CCR7, CXCR4, CCL5, and CCR4 might be hub genes in RA. The different biomarkers and pathways identified in OA and RA may provide references for further study.List of abbreviations: CCL5, C-C motif chemokine ligand 5; CCRs, C-C motif chemokine receptors; CD95, FAS cell surface death receptor; Co-expressed genes, the common genes both in DEGsOA and DEGsRA groups; CXCR4, C-X-C motif chemokine receptor 4; DAVID, Database for Annotation, Visualization, and Integrated Discovery; DEGs, differently expressed genes; DEGsOA, differently expressed genes between osteoarthritis and healthy fibroblast-like synoviocytes; DEGsRA, differently expressed genes between rheumatoid arthritis and healthy fibroblast-like synoviocytes; DLL1, delta-like protein 1

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“…Amino acid substitution may have a substantial effect on SELP function and may be associated with the occurrence of cerebrovascular and cardiovascular disorders. SELP levels and SELP polymorphisms are in the focus of a number of studies as they may provide a new marker to predict future cardiovascular or cerebrovascular events, complications in other inflammatory or oncologic diseases, or even in vitro fertilization failure …”

Section: Introductionmentioning

confidence: 99%

“…A limited number of methods for genotyping the NM_003005.3:c.992G>A (c.992G>A), NM_003005.3:c.1918G>T (c.1918G>T), and NM_003005.3:c.2266A>C (c.2266A>C) SELP polymorphisms (historically named S290N, V599L, and T715P, respectively) are available in the literature and include PCR‐restriction fragment length polymorphism (RFLP), polymerase chain reaction (PCR) with sequence‐specific primers (SSP), mutagenically separated PCR, TaqMan technology‐based real‐time PCR, HRM analysis, and sequencing methods …”

Section: Introductionmentioning

confidence: 99%

“…SELP levels and SELP polymorphisms are in the focus of a number of studies as they may provide a new marker to predict future cardiovascular or cerebrovascular events, complications in other inflammatory or oncologic diseases, or even in vitro fertilization failure. 6,10,[12][13][14][15][16][17][18][19][20][21][22] A limited number of methods for genotyping the analysis, 25 and sequencing methods. 21,22 The PCR-SSP method was previously used in our laboratory, but there was a need for a fast and easy to perform method.…”

Section: Introductionmentioning

confidence: 99%

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Development and validation of a rapid method for genotyping three P‐selectin gene polymorphisms based on high resolution melting analysis

Čeri

Pavić

Horvat

et al. 2018

Clinical Laboratory Analysis

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Background High resolution melting (HRM) analysis is one of the newer, reliable, and sensitive genotyping techniques, which offers considerable time and cost savings. P‐selectin is an adhesion molecule that has a role in the initial phases of leukocyte adhesion to stimulated platelets and endothelial cells in inflammation. Multiple polymorphisms in P‐selectin gene (SELP) that affect the protein sequence have been described. The aim of this study was to design, optimize, and validate a simple and rapid in‐house HRM‐based method for genotyping the NM_003005.3:c.992G>A (c.992G>A), NM_003005.3:c.1918G>T (c.1918G>T), and NM_003005.3:c.2266A>C (c.2266A>C) SELP polymorphisms. Methods Initial genotyping of three SELP polymorphisms was performed by applying polymerase chain reaction (PCR) with sequence‐specific primers (SSP), which was used as a reference method for determination of analytical sensitivity. PCR‐HRM was performed with primers for c.2266A>C reported in the literature. Primers for the remaining two polymorphisms were designed using Primer‐BLAST. Precision testing was performed using three samples with different genotypes. For accuracy, analytical sensitivity and specificity testing, 20 wild type, 10 heterozygous, and 10 homozygous samples were chosen per polymorphism. Results were expressed as percentage of concordance with the acceptability criterion ≥95%. Results Agreement of results was 100% for all validation parameters except for analytical sensitivity for c.1918G>T and c.2266A>C, with agreement of 90%. Repeated analysis using both methods revealed an error in initial genotyping and correct genotyping by PCR‐HRM, which was confirmed by Sanger sequencing. Conclusion The validation confirmed PCR‐HRM as a precise, accurate, and specific method for genotyping the c.992G>A, c.1918G>T, and c.2266A>C SELP polymorphisms.

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Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression

Cited by 23 publications

References 64 publications

Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar

Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar

Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA) based on microarray profiles of human joint fibroblast‐like synoviocytes

Development and validation of a rapid method for genotyping three P‐selectin gene polymorphisms based on high resolution melting analysis

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