Abstract
To investigate the correlation between gene mutation and knee osteoarthritis (KOA), a whole-exome sequencing (WES) was applied to analyze blood samples of four KOA patients and two normal subjects in a family. Gene mutations were identified by gene-trapping and high-throughput sequencing analysis across the differences between the patients and normal subjects. The interactive gene network analysis on the retrieval of interacting genes (STRING) database and the KOA-related genes expression data sets was performed. A possibly detrimental and nonsynonymous mutation at the kallikrein-related peptidase 6 (KLK6) gene (rs201586262, c. C80A, P27H) was identified and attracted our attention. KLK6 belongs to the kallikrein family of serine proteases and its serum level is known as a prevalent biomarker in inflammatory and malignant diseases. KLK6 expresses in the extracellular compartment for matrix degradation, highlighting that KLK6 plays a role in the pathogenesis of KOA. By using the gene databases, the KOA-related genes were mined after de-duplication and IL6 was selected as the most relevant gene through interactive analysis of protein-protein interaction (PPI) network. The data suggested that KLK6 gene mutation and the related expression alteration of IL6 gene might determine the occurrence of hereditary KOA. The is the first study discovering the gene mutation of KLK6 as a factor of pathogenesis of KOA, especially the hereditary KOA.