scholarly journals Rapid knee OA progression is associated with decelerated peripheral blood DNA methylation aging: data from the osteoarthritis initiative

2017 ◽  
Vol 25 ◽  
pp. S39
Author(s):  
M. Jeffries ◽  
A. Rivas
Keyword(s):  
Dna Methylation ◽  
Peripheral Blood ◽  
Knee Oa ◽  
Osteoarthritis Initiative

scholarly journals A pilot study of peripheral blood DNA methylation models as predictors of knee osteoarthritis radiographic progression: data from the Osteoarthritis Initiative (OAI)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christopher M. Dunn ◽  
Michael C. Nevitt ◽  
John A. Lynch ◽  
Matlock A. Jeffries
Keyword(s):  
Dna Methylation ◽  
Pilot Study ◽  
Knee Osteoarthritis ◽  
Peripheral Blood ◽  
Radiographic Progression ◽  
Mononuclear Cells ◽  
Model Performance ◽  
Joint Space ◽  
Peripheral Blood Mononuclear ◽  
Osteoarthritis Initiative

AbstractKnee osteoarthritis (OA) is a leading cause of chronic disability worldwide, but no diagnostic or prognostic biomarkers are available. Increasing evidence supports epigenetic dysregulation as a contributor to OA pathogenesis. In this pilot study, we investigated epigenetic patterns in peripheral blood mononuclear cells (PBMCs) as models to predict future radiographic progression in OA patients enrolled in the longitudinal Osteoarthritis Initiative (OAI) study. PBMC DNA was analyzed from baseline OAI visits in 58 future radiographic progressors (joint space narrowing at 24 months, sustained at 48 months) compared to 58 non-progressors. DNA methylation was quantified via Illumina microarrays and beta- and M-values were used to generate linear classification models. Data were randomly split into a 60% development and 40% validation subsets, models developed and tested, and cross-validated in a total of 40 cycles. M-value based models outperformed beta-value based models (ROC-AUC 0.81 ± 0.01 vs. 0.73 ± 0.02, mean ± SEM, comparison p = 0.002), with a mean classification accuracy of 73 ± 1% (mean ± SEM) for M- and 69 ± 1% for beta-based models. Adjusting for covariates did not significantly alter model performance. Our findings suggest that PBMC DNA methylation-based models may be useful as biomarkers of OA progression and warrant additional evaluation in larger patient cohorts.

scholarly journals Association of accelerated dynamics of telomere sequence loss in peripheral blood leukocytes with incident knee osteoarthritis in Osteoarthritis Initiative cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebeca Guillén ◽  
Fátima Otero ◽  
Alejandro Mosquera ◽  
María Vázquez-Mosquera ◽  
Ignacio Rego-Pérez ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Joint Disease ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Knee Oa ◽  
Age Related ◽  
Telomere Sequence ◽  
Osteoarthritis Initiative ◽  
Telomere Loss

AbstractOsteoarthritis (OA) is a chronic degenerative joint disease, being the main cause of laboral inability. Decreased telomere size in peripheral blood leukocytes (PBL) has been correlated with age-related pathologies, like knee OA. In a dynamic approach, telomere-qPCR was performed to evaluate the relative percentage of PBL telomere loss after a 6-year follow-up, in 281 subjects from the prospective osteoarthritis initiative (OAI) cohort. A radiological Kellgren-Lawrence (KL) grade ≥ 2 was indicative of knee OA. Individuals with knee OA at recruitment (n = 144) showed a higher PBL telomere loss after 6 years than those without knee OA at baseline (n = 137; p = 0.018). Moreover, individuals that developed knee OA during the follow-up (n = 39) exhibited a higher telomere loss compared to those that remained without OA (n = 98; p < 0.001). Logistic regression analysis showed that PBLs telomere loss was not significantly associated with knee OA at recruitment, but behaves as an independent risk factor associated with incidence after follow-up (OR: 1.043; p = 0.041), together with maximum KL grade (OR: 3.627; p = 0.011), body mass index-BMI (OR: 1.252; p < 0.001) and WOMAC-index (OR: 1.247; p = 0.021), at recruitment. The telomere decay in PBLs is faster in individuals with incident knee OA, possibly reflecting a systemic-global accelerated aging that enhances the cartilage degeneration.

scholarly journals Comparison of DNA Methylation Profiles of Hemostatic Genes between Liver Tissue and Peripheral Blood within Individuals

2020 ◽  
Author(s):  
Annelie Angerfors ◽  
Martina Olsson Lindvall ◽  
Björn Andersson ◽  
Staffan Nilsson ◽  
Marcela Davila Lopez ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Peripheral Blood ◽  
Liver Tissue ◽  
Association Studies ◽  
Epidemiological Studies ◽  
Methylation Pattern ◽  
Cpg Dinucleotides ◽  
Phenotypic Differences ◽  
Targeted Bisulfite Sequencing ◽  
Hemostatic Genes

AbstractDNA methylation has become increasingly recognized in the etiology of complex diseases, including thrombotic disorders. Blood is often collected in epidemiological studies for genotyping and has recently also been used to examine DNA methylation in epigenome-wide association studies. DNA methylation patterns are often tissue-specific, thus, peripheral blood may not accurately reflect the methylation pattern in the tissue of relevance. Here, we collected paired liver and blood samples concurrently from 27 individuals undergoing liver surgery. We performed targeted bisulfite sequencing for a set of 35 hemostatic genes primarily expressed in liver to analyze DNA methylation levels of >10,000 cytosine-phosphate-guanine (CpG) dinucleotides. We evaluated whether DNA methylation in blood could serve as a proxy for DNA methylation in liver at individual CpGs. Approximately 30% of CpGs were nonvariable and were predominantly hypo- (<25%) or hypermethylated (>70%) in both tissues. While blood can serve as a proxy for liver at these CpGs, the low variability renders these unlikely to explain phenotypic differences. We therefore focused on CpG sites with variable methylation levels in liver. The level of blood–liver tissue correlation varied widely across these variable CpGs; moderate correlations (0.5 ≤ r < 0.75) were detected for 6% and strong correlations (r ≥ 0.75) for a further 4%. Our findings indicate that it is essential to study the concordance of DNA methylation between blood and liver at individual CpGs. This paired blood–liver dataset is intended as a resource to aid interpretation of blood-based DNA methylation results.

scholarly journals Gait Speed as a Predictor for Diabetes Incidence in People with or at Risk of Knee Osteoarthritis: A Longitudinal Analysis from the Osteoarthritis Initiative

2021 ◽  
Vol 18 (9) ◽  
pp. 4414
Author(s):  
Aqeel M. Alenazi ◽  
Bader A. Alqahtani ◽  
Vishal Vennu ◽  
Mohammed M. Alshehri ◽  
Ahmad D. Alanazi ◽  
...  
Keyword(s):  
At Risk ◽  
Gait Speed ◽  
Area Under The Curve ◽  
Incident Diabetes ◽  
Future Research ◽  
Cutoff Score ◽  
Diabetes Incidence ◽  
Knee Oa ◽  
Osteoarthritis Initiative

Background: This study examined the association between baseline gait speed with incident diabetes mellitus (DM) among people with or at elevated risk for knee OA. Materials and Methods: Participants from the Osteoarthritis Initiative, aged 45 to 79 years, where included. Participants with or at risk of knee OA from baseline to the 96-month visit were included. Participants with self-reported DM at baseline were excluded. DM incidence was followed over the 4-time points. Gait speed was measured at baseline using a 20-m walk test. Generalized estimating equations with logistic regression were utilized for analyses. Receiver operator characteristic curves and area under the curve were used to determine the cutoff score for baseline speed. Results: Of the 4313 participants included in the analyses (58.7% females), 301 participants had a cumulative incidence of DM of 7.0% during follow-up. Decreased gait speed was a significant predictor of incident DM (RR 0.44, p = 0.018). The threshold for baseline gait speed that predicted incident DM was 1.32 m/s with an area under the curve of 0.59 (p < 0.001). Conclusions: Baseline gait speed could be an important screening tool for identifying people at risk of incident diabetes, and the determined cutoff value for gait speed should be examined in future research.

scholarly journals One year change of knee cartilage morphology in the first release of participants from the Osteoarthritis Initiative progression subcohort: association with sex, body mass index, symptoms and radiographic osteoarthritis status

2008 ◽  
Vol 68 (5) ◽  
pp. 674-679 ◽  
Author(s):  
F Eckstein ◽  
S Maschek ◽  
W Wirth ◽  
M Hudelmaier ◽  
W Hitzl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Body Mass ◽  
Statistical Significance ◽  
Weight Bearing ◽  
Rate Of Change ◽  
Cartilage Loss ◽  
Knee Oa ◽  
Symptomatic Knee ◽  
Osteoarthritis Initiative

Objective:The Osteoarthritis Initiative (OAI) is a multicentre study targeted at identifying biomarkers for evaluating the progression and risk factors of symptomatic knee OA. Here cartilage loss using 3 Tesla (3 T) MRI is analysed over 1 year in a subset of the OAI, together with its association with various risk factors.Methods:An age- and gender-stratified subsample of the OAI progression subcohort (79 women and 77 men, mean (SD) age 60.9 (9.9) years, body mass index (BMI) 30.3 (4.7)) with both frequent symptoms and radiographic OA in at least one knee was studied. Coronal FLASHwe (fast low angle shot with water excitation) MRIs of the right knee were acquired at 3 T. Seven readers segmented tibial and femoral cartilages blinded to order of acquisition. Segmentations were quality controlled by one expert.Results:The reduction in mean cartilage thickness (ThC) was greater (p = 0.004) in the medial than in the lateral compartment, greater (p = 0.001) in the medial femur (−1.9%) than in the medial tibia (−0.5%) and greater (p = 0.011) in the lateral tibia (−0.7%) than in the lateral femur (0.1%). Multifactorial analysis of variance did not reveal significant differences in the rate of change in ThC by sex, BMI, symptoms and radiographic knee OA status. Knees with Kellgren–Lawrence grade 2 or 3 and with a BMI >30 tended to display greater changes.Conclusions:In this sample of the OAI progression subcohort, the greatest, but overall very modest, rate of cartilage loss was observed in the weight-bearing medial femoral condyle. Knees with radiographic OA in obese participants showed trends towards higher rates of change than those of other participants, but these trends did not reach statistical significance.

scholarly journals Multidimensional prognostic index and the risk of fractures: an 8-year longitudinal cohort study in the Osteoarthritis Initiative

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicola Veronese ◽  
Lee Smith ◽  
Ekaterini Zigoura ◽  
Mario Barbagallo ◽  
Ligia J. Dominguez ◽  
...  
Keyword(s):  
Older People ◽  
Fracture Risk ◽  
Geriatric Assessment ◽  
Comprehensive Geriatric Assessment ◽  
Prognostic Index ◽  
Knee Oa ◽  
Increased Risk ◽  
Cox's Regression ◽  
Clinical Fractures ◽  
Osteoarthritis Initiative

Abstract Summary In this longitudinal study, with a follow-up of 8 years, multidimensional prognostic index (MPI), a product of the comprehensive geriatric assessment, significantly predicted the onset of fractures in older people affected by knee osteoarthritis. Purpose Frailty may be associated with higher fracture risk, but limited research has been carried out using a multidimensional approach to frailty assessment and diagnosis. The present research aimed to investigate whether the MPI, based on comprehensive geriatric assessment (CGA), is associated with the risk of fractures in the Osteoarthritis Initiative (OAI) study. Methods Community-dwellers affected by knee OA or at high risk for this condition were followed-up for 8 years. A standardized CGA including information on functional, nutritional, mood, comorbidity, medication, quality of life, and co-habitation status was used to calculate the MPI. Fractures were diagnosed using self-reported information. Cox’s regression analysis was carried out and results are reported as hazard ratios (HRs), with their 95% confidence intervals (CIs), adjusted for potential confounders. Results The sample consisted of 4024 individuals (mean age 61.0 years, females = 59.0%). People with incident fractures had a significant higher MPI baseline value than those without (0.42 ± 0.18 vs. 0.40 ± 0.17). After adjusting for several potential confounders, people with an MPI over 0.66 (HR = 1.49; 95%CI: 1.11–2.00) experienced a higher risk of fractures. An increase in 0.10 point in MPI score corresponded to an increase in fracture risk of 4% (HR = 1.04; 95%CI: 1.008–1.07). Higher MPI values were also associated with a higher risk of non-vertebral clinical fractures. Conclusion Higher MPI values at baseline were associated with an increased risk of fractures, reinforcing the importance of CGA in predicting fractures in older people affected by knee OA.

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