Open Access Open Badges Research article

Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility

Luigi Minafra1*, Valentina Bravatà1, Michele Saporito2, Francesco P Cammarata1, Giusi I Forte1, Salvatore Caldarella1, Michele D’Arienzo2, Maria C Gilardi134, Cristina Messa145 and Filippo Boniforti6

Author Affiliations

1 IBFM CNR-LATO, Contrada Pietrapollastra Pisciotto, 90015 Cefalù, PA, Italy

2 Clinica Ortopedica e Traumatologica, Policlinico Universitario P. Giaccone-Università degli Studi di Palermo, via del Vespro 143, 90127 Palermo, Italy

3 Nuclear Medicine, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy

4 Department of Health Sciences, Tecnomed Foundation, University of Milano-Bicocca, via Pergolesi 33, 20900 Monza (MB), Italy

5 Nuclear Medicine Center, San Gerardo Hospital, via Pergolesi 33, 20900 Monza (MB), Italy

6 Unità Operativa di Ortopedia, San Raffaele Hospital ‘G. Giglio’, Contrada Pietrapollastra Pisciotto, 90015 Cefalù (PA), Italy

For all author emails, please log on.

Arthritis Research & Therapy 2014, 16:R91  doi:10.1186/ar4535

Published: 9 April 2014



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.


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.


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.


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.