Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility

Abstract

IntroductionOsteoarthritis (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.MethodsIn 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.ResultsIn 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.ConclusionsThis 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.

Genetic influence of growth and differentiation factor 5 gene polymorphism (+104T/C) on the development of knee osteoarthritis and its association with disease severity

“…Our results were also consistent with the results of the study conducted by Minafra et al (26) that indicated the presence of an association between the presence of the TT genotype and radiological severity of KOA represented by the K-L score (p=0.02).…”

“…The grading of OA is based on the radiological classification of the K-L score and is usually aided by other general or specific joint clinical and functional scores (26)(27).…”

Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts. A meta-analysis and functional study

“…Thus, the pathogenesis of OA is still unclear; however, it is widely accepted that genetics plays a main role in the prevalence and progression of this disease;4 even prediction tools for knee OA based on genetic and clinical information have been developed 5 6. Besides, during the last years, increasing evidence points to the implication of the mitochondria and the mitochondrial DNA (mtDNA) haplogroups in the pathogenesis of the disease 2 7 8…”

Clinical significance of Matrilin-3 gene polymorphism in Egyptian patients with primary knee osteoarthritis

“…In vitro studies of MATN-3 identified its anti-anabolic and pro-catabolic functions, suggesting that it plays an important role in OA (22,23 Two studies conducted by Vincourt et al (25,26) revealed higher levels of MATN-3 in both the serum and synovial fluid of OA patients.…”