Dataset Information

Genetic Contribution to the Development of Radiographic Knee Osteoarthritis in a Population Presenting with Nonacute Knee Symptoms a Decade Earlier.

ABSTRACT: This study examined the contribution of the osteoarthritis (OA) susceptibility genes ASPN, GDF5, DIO2, and the 7q22 region to the development of radiographic knee OA in patients with a mean age of 40.6 ± 7.9 years (standard deviation) and who suffered from nonacute knee complaints a decade earlier. Dose-response associations of four single nucleotide polymorphisms(SNPs) in the susceptibility genes were determined by comparing 36 patients who showed the development of OA on radiographs (Kellgren and Lawrence score ?1) with 88 patients having normal cartilage with no development of OA on radiographs. Multivariate logistic regression analysis including the variables such as age, gender, body mass index, and reported knee trauma was performed. A dose-response association of DIO2 SNP rs225014: odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1-4.5 (P = 0.019) and GDF5 SNP rs143383: OR 2.0, 95% CI 1.1-3.8 (P = 0.031) was observed with knee OA development. The ASPN and 7q22 SNPs were not associated with OA development.

SUBMITTER: Huetink K

PROVIDER: S-EPMC4854216 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Genetic Contribution to the Development of Radiographic Knee Osteoarthritis in a Population Presenting with Nonacute Knee Symptoms a Decade Earlier.

Huétink Kasper K van der Voort Paul P Bloem Johan L JL Nelissen Rob G H H RG Meulenbelt Ingrid I

Clinical medicine insights. Arthritis and musculoskeletal disorders 20160428

This study examined the contribution of the osteoarthritis (OA) susceptibility genes ASPN, GDF5, DIO2, and the 7q22 region to the development of radiographic knee OA in patients with a mean age of 40.6 ± 7.9 years (standard deviation) and who suffered from nonacute knee complaints a decade earlier. Dose-response associations of four single nucleotide polymorphisms(SNPs) in the susceptibility genes were determined by comparing 36 patients who showed the development of OA on radiographs (Kellgren ...[more]

PMID: 27158223

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Project description:BackgroundAlthough cross-sectional and cohort data suggest that higher serum blood glucose levels in patients with knee osteoarthritis (KOA) are associated with more severe knee symptoms, little is known about the longitudinal relationship between serum blood glucose and knee symptoms, particularly considering central sensitization (CS) comorbidity, which also worsens knee symptoms.MethodsWe evaluated the longitudinal relationship between serum blood glucose and knee symptoms by dividing the cohort of patients with KOA into those with and without CS. We hypothesized that higher serum blood glucose levels would worsen knee symptoms. A total of 297 participants (mean age: 59.6 years; females: 211; average BMI: 23.7 kg/m2) were enrolled in this study. At baseline, plain radiographs of the bilateral knee joints were evaluated according to the Kellgren-Lawrence grade (KLG). All participants exhibited at least a KLG ≥ 2 in each knee. At baseline, fasting blood glucose (FBG) and Central Sensitization Inventory-9 (CSI-9) were evaluated; ≥ 10 points on the CSI-9 was defined as CS+. Knee injury and Osteoarthritis Outcome Score (KOOS) was evaluated at baseline and at 1-year follow-up; the change in KOOS (ΔKOOS) was calculated by subtracting the KOOS at baseline from that at the 1-year follow-up. Multiple linear regression analysis was conducted with ΔKOOS as the dependent variable and FBG at baseline as the independent variable, adjusted for age, sex, BMI, and CSI-9 at baseline.ResultsOf the 297 subjects, 48 (16.2 %) were defined as CS+. In the CS - group, there was no association between FBG levels at baseline and ΔKOOS. In contrast, FBG at baseline was negatively associated with ΔKOOS pain (B = - 0.448; p = 0.003), ADL (B = - 0.438; p = 0.003), and sports (B = - 0.706; p = 0.007).ConclusionsIn patients with radiographic KOA and CS, higher blood glucose levels were associated with deteriorated knee symptoms during the 1-year follow-up. Healthcare providers should pay attention to controlling blood glucose, particularly in patients with KOA and concurrent CS, to mitigate their knee symptoms.Study designRetrospective cohort study (evidence level: III).

Project description:INTRODUCTION: Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals. METHODS: In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis. RESULTS: In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features. CONCLUSIONS: This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.

Dataset Information

Genetic Contribution to the Development of Radiographic Knee Osteoarthritis in a Population Presenting with Nonacute Knee Symptoms a Decade Earlier.

Publications

Genetic Contribution to the Development of Radiographic Knee Osteoarthritis in a Population Presenting with Nonacute Knee Symptoms a Decade Earlier.

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