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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89223 |
| Date | 24 January 2024 |
| Creators | Huber, René, Kirsten, Holger, Näkki, Annu, Pohlers, Dirk, Thude, Hansjörg, Eidner, Thorsten, Heinig, Matthias, Brand, Korbinian, Ahnert, Peter, Kinne, Raimund W. |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1382 |
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