Association of TGFβ1 Gene Polymorphisms with Early Onset Primary Knee Osteoarthritis in South Indians: Case-Control Study from a Cosmopolitan City

Special Article - Osteoarthritis

Austin Orthop. 2018; 3(1): 1007.

Association of TGFβ1 Gene Polymorphisms with Early Onset Primary Knee Osteoarthritis in South Indians: Case-Control Study from a Cosmopolitan City

Poornima S1,2, Subramanyam K3,4, Iyer GR¹, Darooei M¹, Daram S², Sumanlatha G³ and Hasan Q¹*

¹Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, Telangana, India

²Department of Genetics and Molecular Medicine, Kamineni Life Sciences, Hyderabad, Telangana, India

³Department of Orthopedics, Kamineni Hospitals, Hyderabad, Telangana, India

4Department of Orthopedics, Yashoda Hospitals, Hyderabad, Telangana, India

5Department of Genetics, Osmania University, Hyderabad, Telangana, India

*Corresponding author: Qurratulain Hasan, Department of Genetics & Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad, Telangana, India

Received: March 03, 2018; Accepted: April 06, 2018; Published: April 13, 2018


Osteoarthritis (OA) is multifactorial disease manifested by synovial inflammation and cartilage damage leads to joint swelling and pain. OA involving synovium, bone and cartilage. The main characteristics of OA are cartilage damage, synovial fibrosis, subchondral bone sclerosis and osteophyte formation which is clinically characterized by pain, tenderness, limitation of joint movement and loss of function. Transforming Growth Factor β1 (TGFβ1) gene is a multifunctional cytokine that plays a major role in normal cellular process. It plays a role in development and homeostasis of various tissues. They regulate cell proliferation, differentiation, apoptosis and migration. Family studies indicated that there is a relation between genetically determined factors and the development of osteoarthritis. The aim of the present study was to analyse the common TGFβ1–C509T promoter polymorphism and TGFβ1 T869C polymorphisms in South Indians and to investigate their association with early onset primary knee osteoarthritis. This study was approved by Institutional Ethics Committee. The study involved 200 early primary knee OA cases which are clinically diagnosed and radiologically confirmed along with age and gender matched controls. For polymorphism –C509T a significant difference in the T allele frequency was observed between cases and controls (p<0.0001) and TT genotype also showed statistical significance with the disease (p<0.0001). For T869C polymorphism C allele and CC genotype showed statistical significance with early onset primary knee osteoarthritis (p=<0.05). These SNPs rs1800469 and rs1982073are associated with early onset primary knee OA and could be used as potential biomarkers to identify individuals/family members, who are at risk of developing knee OA to plan preventative strategies in our population, after confirming in a larger study group. This will help reduce morbidity and disability associated with this pathology. To the best of our knowledge this is the first study in India.


Osteoarthritis (OA) is a musculoskeletal disease characterized by gradual thinning and loss of articular cartilage of the synovial joints with a concurrent alteration in the physiology of several other joint tissues including the subchondral bone and the synovium [1,2]. The bone cartilage is an important synergistic unit consisting of the area between the deep layers of articular cartilage and the underlying subchondral bone [3]. There have been many attempts to identify and grade OA and the most widely used method is the Kellgren and Lawrence (K&L) score. The overall grades of severity are determined on a score of 0-4 and are based on the sequential appearance of osteophytes, joint space loss, sclerosis, criptus and cysts.

OA is predicted to be the single greatest cause of disability in the general population. In most ethnic groups OA is extremely common with its prevalence varying, depending on the diagnostic criteria used and the joint examined [4]. OA has a prominent and determental impact on wellbeing with up to one fifth of the affected individuals giving up work because of the disease and this increased morbidity contributes indirectly to an increased mortality [5].

The close physical association between subchondral bone and cartilage in the joints allows interaction and suggests that a biochemical and molecular crosstalk may contribute to OA pathology [6].

The role of specific genes is under investigation as the estimated heritability of primary OA is high showing i.e. 40% for the knee, 60% for the hip, and 65% for the hand [7]. It is estimated that OA is the second most common rheumatological problem and is the most frequent joint disease with prevalence of 17 to 60.6% in India [8], Sharma et al, 2007. There are currently no pharmacological interventions for patients with OA. Total joint replacement is the only effective treatment of end stage disease which is invasive and relatively expensive. It would be particularly beneficial therefore to identify novel therapeutic targets within OA pathways to improve patient outcomes. It has been postulated that the best biomarkers for osteoarthritis are most likely to be structural molecules or fragments linked to cartilage bone or synovium which may be specific to one type of joint tissue or common to them all. They may represent tissue degradation or tissue synthesis and may be measured in synovial fluid, blood or urine [9], Karsdal et al. Molecular genetics investigations have gained an increasingly significant understanding role in the knowledge of OA and have provided evidence for a genetic component for this pathology [10,11].

Genome wide association studies revealed that susceptibility to OA is influenced by genetic predisposition. It has become apparent that many of these OA susceptibility loci, have particular relevance for the disease development at specific skeletal sites and furthermore some loci could be linked to the disease depending on ethnic differences [12-14].

In this case control study we demonstrated the association with two different SNPs of Transforming Growth Factor (TGFβ1) gene polymorphisms with early onset primary knee osteoarthritis.

TGFβ1 protein has been localized in developing cartilage, endochondrial and membrane bone and skin suggesting its role in the growth and differentiation of these tissues. TGFβ1 is pleiotrophic cytokine that is important in the regulation of joint homeostasis and disease. Lack of TGFβ1 signaling results in predisposition damage of cartilage, therefore TGFβ supplementation will help in cartilage maintenance [15].

A TGFβ1 level differs greatly between healthy joints, where it is low and in osteoarthritic joints where it is high. Being low in healthy joints and high in osteoarthritic joints leading to the activation of different signaling pathways in joint cells [15]. TGFβ1 counteracts pathological changes in a young healthy joint, alters its signaling during ageing and is a driving force of pathology in osteoarthritic joints [16,26]. Study postulated that TGFβ1gene signaling demonstrate that it plays a critical role during OA development.

It is a hospital based case control study to evaluate the association of two TGFβ1 gene polymorphism in early onset primary knee osteoarthritis and its correlation with body mass index in our Indian patients.