Background. Кnee osteoarthritis (OA) is a multifactorial disease in which genetic factors play an important role. The share of the hereditary component in the development of OA, according to various literature sources, ranges from 40 to 65%. Кnee OA is a progressive disease that leads to a decrease in the quality of life and disability.
 The study aimed to evaluate the role of polymorphic markers of candidate genes rs2820436 and rs2820443 LYPLAL1, rs3771501 TGFA, rs11177 GNL3, rs6976 GLT8D1 in the progression of knee OA in the population of the Central Chernozem Region of Russia.
 Methods. The study was performed in a case-control design on a sample of 500 patients with knee OA. Case patients with III-IV stages of the disease according to KellgrenLawrence (n = 325), control (individuals who do not have the analyzed sign III-IV stages of the disease) patients with stage II (n = 175). Genotyping of five single nucleotide polymorphisms (SNPs) of candidate genes was performed using the polymerase chain reaction method for DNA synthesis. The study of the associations of the studied polymorphic loci, the calculation of haplotype frequencies and the analysis of their relationship with the progression of knee OA was carried out by the method of logistic regression in the program PLINK v 2.050.
 Results. Significant associations with the progression of OA of the knee were established for allelic variant A rs2820436 of LYPLAL1 gene according to allelic (OR = 1.48, p = 0.010, pperm = 0.012), additive (OR = 1.58, p = 0.009, pperm = 0.010), dominant (OR = 1.61, p = 0.024, pperm = 0.030) genetic models and A/A genotype of the same polymorphism (OR = 2.53, p = 0.041). The genotypes C/C rs2820436 LYPLAL1 (OR = 0.67, p = 0.043), A/G rs3771501 TGFA (OR = 0.67, p = 0.042) have a protective role in the progression of the disease. It was found that the frequency of the AC haplotype of haploblock rs2820436-rs2820443 in the group of patients with III-IV stages of the disease was significantly higher than in patients with stage II (OR = 1.83, p = 0.002, pperm = 0.002). The identified molecular genetic markers rs2820436 and rs2820443 of LYPLAL1 gene, rs3771501 of TGFA gene are associated both with the risk of developing OA according to previous genome-wide studies and, according to our data, are associated with the progression of knee OA.
 Conclusions. Genetic risk factors for the development of knee OA of III-IV radiological stages are allelic variant A and genotype A/A rs2820436 of LYPLAL1 gene, haplotype AC of haploblock rs2820436-rs2820443 in the population of the Central Chernozem Region of Russia. Genotypes C/C rs2820436 of LYPLAL1 gene and A/G rs3771501 of TGFA gene have a protective value in the progression of this disease.