Association of Human FOS Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study.
Int J Mol Sci
; 20(6)2019 Mar 19.
Article
em En
| MEDLINE
| ID: mdl-30893847
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) 1.2â»3.7, p = 0.0086). This association was successfully replicated in the Finnish Health 2000 study cohort (allelic OR 1.72, 95% CI 1.2â»2.5, p = 0.006). FOS Promoter variants may represent relevant susceptibility markers for knee-OA.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regiões Promotoras Genéticas
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Proteínas Proto-Oncogênicas c-fos
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Osteoartrite do Joelho
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Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
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Estudos de Associação Genética
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article