Dataset Information

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

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.

SUBMITTER: Huber R

PROVIDER: S-EPMC6471183 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Huber René R Kirsten Holger H Näkki Annu A Pohlers Dirk D Thude Hansjörg H Eidner Thorsten T Heinig Matthias M Brand Korbinian K Ahnert Peter P Kinne Raimund W RW

International journal of molecular sciences 20190319 6

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 ...[more]

PMID: 30893847

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Project description:ObjectivesThe aim of this study was to investigate changes over time in osteoarthritis risk factors most closely associated with the occurrence of total knee arthroplasty (TKA). We hypothesize that the robustness of a longitudinal case-control study will provide new information on the association between changes in various clinical and structural parameters in different time frames before TKA.MethodsCases (195; TKA after cohort entry) and controls (468) matched for age, gender, income, WOMAC pain, Kellgren-Lawrence grade and follow-up duration were from the Osteoarthritis Initiative cohort. Associations between changes in sociodemographic, clinical, imaging and osteoarthritis therapies with the occurrence of TKA were performed using conditional logistic regression analyses.ResultsWorsening of WOMAC scores (cOR 1.02-1.20, p ⩽ 0.012), KOOS (1.02-1.04, p ⩽ 0.014), knee injuries sustained in the previous 30-40 years (women 2.70, p = 0.034) and valgus alignment (1.10, p = 0.052) were associated with the occurrence of TKA. Also associated with TKA was cartilage volume loss in the lateral (overall 1.76, p = 0.025; women 1.93, p = 0.047) and medial compartments (⩾10%, overall 1.54, p = 0.027; men 2.34, p = 0.008), occurrence of medial meniscal extrusion (overall 1.77, p = 0.046; men 2.86, p = 0.028), and increase in bone marrow lesions (BMLs) for women (1.09, p = 0.048). The association of risk factors with TKA was reinforced when both an increase in WOMAC pain and cartilage volume loss (1.85, p = 0.001) were combined. Pain medication usage, mainly narcotics and intra-articular steroid injections (IASI), was also associated with TKA, with no impact on changes in cartilage loss or structure.ConclusionThis study provides new information about gender differences in risk factors associated with the occurrence of TKA. Worsening of valgus alignment, cartilage volume loss in the lateral compartment, BMLs and older injuries are important risk factors in women, while medial compartment cartilage loss and meniscal extrusion are in men. The use of pain medication and IASI although associated was found not causal with TKA.

Dataset Information

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

Publications

Association of Human <i>FOS</i> Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study.

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