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Objectives.  To investigate associations of selected single-nucleotide polymorphisms (SNPs) in  ADAM12  gene with radiographic knee osteoarthritis (rKOA) in Estonian population.  Methods.  The rs3740199, rs1871054, rs1278279, and rs1044122 SNPs in  ADAM12  gene were genotyped in 438 subjects (303 women) from population-based cohort, aged 32 to 57 (mean 45.4). The rKOA features were evaluated in the tibiofemoral joint (TFJ) and patellofemoral joint.  Results.  The early rKOA was found in 51.4% of investigated subjects (72% women) and 12.3% of participants (63% women) had advanced stage of diseases. The A allele of synonymous SNP rs1044122 was associated with early rKOA in TFJ, predominantly with the presence of osteophytes in females (OR 1.57; 95% CI 1.08–2.29,  P  = 0.018). The C allele of intron polymorphism rs1871054 carried risk for advanced rKOA, mostly to osteophyte formation in TFJ in males (OR 3.03; 95% CI 1.11–7.53,  P  = 0.018). Also the CCAA haplotype of  ADAM12  was associated with osteophytosis, again mostly in TFJ in males ( P  = 0.014). For rs3740199 and rs1278279, no statistically significant associations were observed.  Conclusion.     ADAM12  gene variants are related to rKOA risk during the early and late stages of diseases. The genetic risk seems to be predominantly associated with the appearance of osteophytes—a marker of bone remodelling and neochondrogenesis.

Two Single-Nucleotide Polymorphisms in ADAM12 Gene Are Associated with Early and Late Radiographic Knee Osteoarthritis in Estonian Population