Genetic Insights of Primary knee osteoarthritis

Abstract

Introduction: Knee Osteoarthritis (KOA) is charecterised by focal loss of joint articular cartilage, osteophyte formation and sub chondral bone remodelling. Common clinical symptoms include pain, stiffness, limitation of the joint movement and swelling. OA is the most common joint disease worldwide and the knee is the common site involved. Classical risk factors of OA include age, gender, weight, joint injury, trauma. However, family history/Hereditary component is the one of the crucial factors. knee OA is a complex disease with environmental and genetic factors associated with its development and progression. Hypotheses: It is classified as primary when no discernible cause is evident and secondary when a triggering factor is apparent. However primary OA possesses significant genetic component. Despite the fact that OA is a late onset advanced age disease the increasing incidence of OA individuals below the age of 55 years and the fact that the several members of the same family are affected suggest a genetic predisposition. Hence, there is a need to identify molecular biomarkers associated with primary early knee osteoarthritis Methods: Several Genome wide association studies and candidate gene studies have identified genetic variants involved in the pathogenesis of OA like VDR, MMP, TGF, GDF5, COL11A1 and VEGF. Currently, the majority of genetic association studies on disease risk focused on identifying the individual’s effect on single nucleotide polymorphisms (SNPs). Results: In the present study, ten gene polymorphisms were studied in Indian population. They are COL21, CRTL1, CRTM, ACE, VDR, GDF5, COG5, CYBA, SREBP2 and TGFβ1 genes which were selected based on their role in cartilage maintenance and bone remodelling. This is the first study in India which looked at the gene polymorphisms. Altogether 100 clinically diagnosed and radiologically confirmed early primary knee OA (KOA) cases and 100 controls with no musculoskeletal diseases, were recruited and molecular analysis was performed by routine PCR - RFLP techniques. Results indicated that COL21, CRTL1, ACE, GDF5, COG5, CYBA, SREBP2 and TGFβ1gene polymorphisms showed an association with the disease where as CRTM and VDR lack of association. Conclusion: These gene polymorphisms can be used as molecular biomarkers for identifying the individuals who are at risk of developing the disease ( primary knee osteoarthritis) and these molecular genotypes helps us in planning tailored treatment and management. It also help us to identify individuals who are at risk of developing knee osteoarthritis and preventive measures can be planned accordingly. To the best of our knowledge this is the first study in India which assessed these ten gene polymorphisms with primary early knee osteoarthritis.