scholarly journals Association of Human FOS Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study

2019 ◽  
Vol 20 (6) ◽  
pp. 1382 ◽  
Author(s):  
René Huber ◽  
Holger Kirsten ◽  
Annu Näkki ◽  
Dirk Pohlers ◽  
Hansjörg Thude ◽  
...  
Keyword(s):  
Gene Expression ◽  
Knee Osteoarthritis ◽  
Reporter Gene ◽  
Reporter Gene Expression ◽  
Study Cohort ◽  
Nucleotide Polymorphisms ◽  
Promoter Snps ◽  
Knee Oa ◽  
Homozygous Genotype ◽  
Screening Population

Our aim was to analyse (i) the presence of single nucleotide polymorphisms (SNPs) in the JUN and FOS core promoters in patients with rheumatoid arthritis (RA), knee-osteoarthritis (OA), and normal controls (NC); (ii) their functional influence on JUN/FOS transcription levels; and (iii) their associations with the occurrence of RA or knee-OA. JUN and FOS promoter SNPs were identified in an initial screening population using the Non-Isotopic RNase Cleavage Assay (NIRCA); their functional influence was analysed using reporter gene assays. Genotyping was done in RA (n = 298), knee-OA (n = 277), and NC (n = 484) samples. For replication, significant associations were validated in a Finnish cohort (OA: n = 72, NC: n = 548). Initially, two SNPs were detected in the JUN promoter and two additional SNPs in the FOS promoter in perfect linkage disequilibrium (LD). JUN promoter SNP rs4647009 caused significant downregulation of reporter gene expression, whereas reporter gene expression was significantly upregulated in the presence of the FOS promoter SNPs. The homozygous genotype of FOS promoter SNPs showed an association with the susceptibility for knee-OA (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.2–3.7, p = 0.0086). This association was successfully replicated in the Finnish Health 2000 study cohort (allelic OR 1.72, 95% CI 1.2–2.5, p = 0.006). FOS Promoter variants may represent relevant susceptibility markers for knee-OA.

Reporter Gene Expression in G2 of the 1-Cell Mouse Embryo

1993 ◽  
Vol 156 (2) ◽  
pp. 552-556 ◽  
Author(s):  
Prahlad T. Ram ◽  
Richard M. Schultz
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Mouse Embryo ◽  
Reporter Gene Expression ◽  
Cell Mouse Embryo

Tetracycline-regulated reporter gene expression in the moss Physcomitrella patens

1996 ◽  
Vol 30 (1) ◽  
pp. 199-205 ◽  
Author(s):  
Mathias Zeidler ◽  
Christiane Gatz ◽  
Elmar Hartmann ◽  
Jon Hughes
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Physcomitrella Patens ◽  
Reporter Gene Expression

The maize GapC4 promoter confers anaerobic reporter gene expression and shows homology to the maize anthocyanin regulatory locus C1

1995 ◽  
Vol 29 (6) ◽  
pp. 1293-1298 ◽  
Author(s):  
Uwe K�hler ◽  
Marie-Fran�oise Liaud ◽  
Ralf R. Mendel ◽  
R�diger Cerff ◽  
Reinhard Hehl
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Reporter Gene Expression ◽  
Regulatory Locus

Abstract 117: MicroRNA-138 regulates S100A1 in Endothelial Cells

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Anagha Sen ◽  
Shumei Ren ◽  
Jianxin Sun ◽  
Patrick Most ◽  
Karsten Peppel
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Reporter Gene ◽  
Recombinant Adenovirus ◽  
Limb Ischemia ◽  
Bioinformatic Analysis ◽  
Reporter Gene Expression ◽  
Luciferase Reporter ◽  
C2c12 Myotubes ◽  
Luciferase Reporter Construct

Rationale: The EF-hand Ca2+ sensor S100A1 is essential for proper endothelial nitric oxide (NO) synthase (eNOS) activation. S100A1 levels are greatly reduced in endothelial cells (ECs) subjected to hypoxia, rendering them dysfunctional. Objective: To determine if the 3’UTR mediates the rapid hypoxia-induced downregulation of S100A1 in ECs. Methods and Results: ECs transfected with a S100A1 - 3’ untranslated region (UTR) luciferase reporter construct displayed significantly reduced gene expression when subjected to gas or chemical hypoxia. Bioinformatic analysis suggested that microRNA -138 (miR-138) could target the 3’UTR of S100A1. Hypoxia greatly increased miR-138 levels in ECs, but not in skeletal muscle C2C12 myotubes. Consistent with this finding, patients with critical limb ischemia (CLI) or mice subjected to femoral artery resection (FAR) displayed increased miR-138 levels. Transfection of a miR-138 mimic into ECs reduced S100A1 - 3 ‘UTR reporter gene expression, while transfection of an anti miR-138 (antagomir) prevented the hypoxia-induced downregulation of the reporter gene. The increased levels of miR-138 are dependent on Hif1-α activation as treatment with siRNA against Hif1-α prevented S100A1 reporter gene downregulation after hypoxia. Conversely, specific activation of Hif1-α by a selective prolyl-hydroxylase inhibitor (IOX2) reduced reporter gene expression. Finally, ECs transfected with miR-138 mimic displayed reduced tube formation when plated onto Matrigel matrix and expressed less NO when stimulated with VEGF. These effects were reversed by gene transfer of S100A1 using recombinant adenovirus. Conclusions: Our study shows that miR-138 is an essential mediator of EC dysfunction via its ability to target the 3’UTR of S100A1 in a hypoxia-induced manner. MiR-138 might thus be an attractive target for the treatment of pathologies that are linked to endothelial dysfunction.

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