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, ). 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, ). Also the CCAA haplotype of ADAM12 was associated with osteophytosis, again mostly in TFJ in males ( ). 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. 1. Introduction Osteoarthritis (OA) is the most common joint disorder and represents a leading musculoskeletal health and socioeconomic burden [1]. The knee is one of the most affected sites [2]. Among recognized OA risk factors like age and overweight, the genetic background, as demonstrated in twins, is expected to play the significant role [3]. To date, several genomewide linkage analyses (GWAS) and numerous association studies of candidate genes have been performed to disclose genetic pattern of OA [4]. Despite promising evidence, only few genes like GDF5 and SMAD3 demonstrated proven susceptibility to OA [5] and these genes, in turn, interpret only a small part of the genetic contribution to the disease. Until now, promising but contradictory data are published for the association of a member of disintegrin and metalloproteinase family—ADAM12 with the pathogenesis of OA [6, 7]. ADAM12 is an active proteinase, which is highly expressed in remodelling and fast-growing tissues such as the placenta and malignant tumours [8]. One of the splice variant of ADAM12 was found to be overexpressed in human OA cartilage [9], and recently, we described the elevation of ADAM12 protein in serum of OA patients [10]. Additionally, one
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