Background: Osteoarthritis (OA) is characterized by cartilage matrix degradation and osteophytes formation. Various risk factors have been involved in the pathogenicity of this degenerative joint disorder. Genetic variations in a disintegrin and metalloprotease 12 (ADAM12) may contribute to the vulnerability of OA. Objectives: The aim of present study was to analyze the association between the ADAM12 gene variants and OA predisposition. Methods: Tetra-primers ARMS-PCR was employed, to genotype the ADAM12 gene polymorphisms (rs1044122 and rs1871054) in 400 knee OA patients and equal number of age-matched controls The association between ADAM12 gene variants and OA susceptibility was estimated using the Chi-square, logistic regression, haplotypes and linkage analyses. Results: A significant association of rs1044122 (genotype: P < 0.001, allele: P < 0.001) and rs1871054 (genotype: P = 0.007, allele:P = 0.001) was observed with increased OA susceptibility. The variant genotype of rs1044122 increased OA risk almost twice [odds ratio (OR) =2.20; P = 0.001] and the risk was higher in females (OR=2.43; P = 0.001). The variant genotype of rs1871054 was perceived to double the risk in females (OR=1.97; P = 0.003). The targeted ADAM12 gene polymorphisms, showed significant association with knee OA susceptibility. Females harboring the polymorphisms might be at risk. Conclusion: The targeted ADAM12 gene polymorphisms, showed significant association with knee OA susceptibility. Females harboring the polymorphisms might be at risk. These findings may help in determining the etiology of OA and recognizing the people at risk of developing knee OA. REFERENCES: [1] Ashford S, Williard J (2014) Osteoarthritis: A review. Nurse Pract 39: 1–8. https://doi.org/10.1097/01.NPR.0000445886.71205.c4. [2] Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21: 263–265. https://doi.org/10.1093/bioinformatics/bth457. [3] Bush WS, Moore JH (2012) Chapter 11: Genome-wide association studies. PLoS Comput Biol 8: e1002822. https://doi.org/10.1371/journal.pcbi.1002822. [4] Clarke GM, Anderson CA, Pettersson FH, Cardon LR, Morris AP, Zondervan KT (2011) Basic statistical analysis in genetic case-control studies. Nat Protoc 6: 121–133. https://doi.org/10.1038/nprot.2010.182. [5] Collins A, Ke X (2012) Primer1: primer design web service for tetra-primer ARMS-PCR. Open Bioinform J 6: 55–58. https://doi.org/10.2174/1875036201206010055. [6] Jung JH, Song GG, Kim JH, Choi SJ (2019) Association of single nucleotide polymorphisms in a disintegrin and metalloproteinase 12 gene with susceptibility to knee osteoarthritis: a meta-analysis. Arch Rheumatol 34: 62–70. https://doi.org/10.5606/ArchRheumatol.2019.6726. Acknowledgements: NIL. Disclosure of Interests: None declared.