Minafra Luigi, Bravatà Valentina, Saporito Michele, Cammarata Francesco P, Forte Giusi I, Caldarella Salvatore, D'Arienzo Michele, Gilardi Maria C, Messa Cristina, Boniforti Filippo
Arthritis Res Ther. 2014 Apr 9;16(2):R91. doi: 10.1186/ar4535.
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.
骨关节炎（OA）被认为是一种多因素和多基因疾病，其诊断主要基于临床和影像学检查。已有研究报道了影像学数据与临床状况之间的相关性。然而，很少有研究，尤其是针对白种人的研究，描述凯尔格伦和劳伦斯骨关节炎分级量表（KL）与基因改变之间的关联，以更好地理解骨关节炎的发病机制和易感性。为了更新膝关节骨关节炎的分级，在本研究中，我们评估了西西里岛人群中KL分级、美国膝关节协会评分（AKSS）等临床特征、年龄以及主要骨关节炎易感性（OS）基因多态性之间的关联。
对66例原发性膝关节骨关节炎的西西里岛患者进行临床和影像学评估，采用AKSS的2个亚评分（膝关节评分（KS）和功能评分（FS））以及KL分级。患者还根据年龄进行分类。利用在线人类孟德尔遗传（OMIM）和单核苷酸多态性数据库（dbSNP）短基因变异数据库，选择包含以下多态性的基因区域进行分析：FRZB rs288326和rs7775、MATN3 rs77245812、ASPN D14重复序列、PTHR2 rs76758470、GDF5 rs143383和DVWA rs11718863。采用桑格DNA测序分析获得患者的基因型。
在我们的患者队列中，所有测试的关联（KL与KS、FS和年龄）均报告了分析变量之间的统计学关联。我们观察到，轻度至重度的骨关节炎影像学分级与严重的临床状况和关节功能丧失相关，且症状的严重程度随年龄增加。关于基因分型分析，我们的结果显示KL分级与GDF5 rs143383和DVWA rs11718863基因改变之间存在显著统计学关联。后者还与更严重的影像学分级相关，显示出其作为骨关节炎标志物进展的预测作用。观察到的临床、影像学和基因特征之间的统计学显著关联，提示应扩展主要基于X线特征的膝关节骨关节炎实际分级。
这项工作代表了一种多学科和转化医学方法来研究骨关节炎，其中临床、影像学以及OS5和OS6单核苷酸多态性评估有助于更好地定义骨关节炎的分级和进展，并有助于开发新的治疗方法。
