Background The etiological factors of osteoarthritis are not fully characterized though the pathology of osteoarthritis is well defined. Genome sequencing resulted in identification of several susceptibility loci confirming the genetic association of disease. (1&2)

Objectives In a case-control study, investigate the association of SNP in GDF-5 gene with osteoarthritis knee

Methods 300 cases with knee osteoarthritis and an equal number of age, gender matched healthy controls were included. Cases were diagnosed using the ACR Guidelines of knee osteoarthritis (KOA). Clinical symptoms were assessed with the knee specific WOMAC index and VAS for knee pain. The severity of disease was determined by radiological KL grades (Kellgren Lawren). The informed consent of the patients was obtained for the participation in this study. The study was approved by the Institutional Ethics Committee. The genomic DNA was isolated from blood and polymorphic study was done by polymerase chain reaction (PCR) with restriction fragments length polymorphism (RFLP). All statistical analysis was performed with the SPSS software package (version 16.0 for windows; SPSS Chicago, IL).

Results The GDF-5 (BSiE1) genotypes were found to be present at significantly higher frequency in cases than in controls, resulting in about 1.80 fold increase of OA risk (P Value=0.016). OA knee was found to be significantly associated with BMI (P Value=0.00). A significant association was found with clinical score of knee OA - VAS with poor and good index (P value=0.010 and 0.026 respectively) and in WOMAC with poor index only (P value=0.0040). On stratifying all osteoarthritis subjects into 3 groups according to severity (KL grade 2 minimal, grade 3 moderate and grade 4 severe OA), no significant association was found.

Conclusions GDF5, are now known to be consistently associated with the risk of knee OA, in different population. An association between the +104T/C GDF5 polymorphism with knee OA in Indian population further confirms a strong genetic influence of this SNP in KOA. This can serve as a potential biomarker and a risk factor for KOA. Likewise associations of this SNP with clinical score have again demonstrated the role of genetic polymorphism on GDF-5 in the development and progression of KOA. It may become a gateway for further research into epigenetic of this SNP, highlighting potential pathways for prevention and therapeutic intervention of knee osteoarthritis

1. Miyamoto Y, Mabuchi A, Shi D, Kubo T, Takatori Y, Saito S, Fujioka M, Sudo A, Uchida A, Yamamoto S, Ozaki K, Takigawa M, Tanaka T, Nakamura Y, Jiang Q, Ikegawa S. A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet. 2007 Apr;39(4):529-33.

2. Southam L, Rodriguez-Lopez J, Wilkins JM, Pombo-Suarez M, Snelling S, Gomez-Reino JJ, Chapman K, Gonzalez A, Loughlin J. An SNP in the 5′-UTR of GDF5 is associated with osteoarthritis susceptibility in Europeans and with in vivo differences in allelic expression in articular cartilage. Hum Mol Genet. 2007 Sep 15;16(18):2226-32.

Disclosure of Interest None Declared