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

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Huber , R , Kirsten , H , Näkki , A , Pohlers , D , Thude , H , Eidner , T , Heinig , M , Brand , K , Ahnert , P & Kinne , R W 2019 , ' Association of Human FOS Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study ' , International Journal of Molecular Sciences , vol. 20 , no. 6 , 1382 . https://doi.org/10.3390/ijms20061382

Title: Association of Human FOS Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study
Author: Huber, Rene; Kirsten, Holger; Näkki, Annu; Pohlers, Dirk; Thude, Hansjoerg; Eidner, Thorsten; Heinig, Matthias; Brand, Korbinian; Ahnert, Peter; Kinne, Raimund W.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2019-03-19
Language: eng
Number of pages: 13
Belongs to series: International Journal of Molecular Sciences
ISSN: 1422-0067
URI: http://hdl.handle.net/10138/301570
Abstract: 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.
Subject: AP-1
JUN
FOS
promoter
knee osteoarthritis
SINGLE-BASE EXTENSION
RHEUMATOID-ARTHRITIS
SYNOVIAL FIBROBLASTS
CELL-PROLIFERATION
C-FOS
EXPRESSION
CLASSIFICATION
PATHOGENESIS
1182 Biochemistry, cell and molecular biology
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