It is known that Osteoarthritis (OA) is a common chronic disease of the musculoskeletal system, which leads to a significant loss of working capacity and disability of people of working age, which worsens the quality of life of the population and causes economic burden and losses to all countries of the world. In addition, OA is known as a disease with an inherent high level of comorbidity. Scientists single out diseases of cardiovascular diseases, digestive systems and metabolic disorders as those that are most often combined with OA and complicate the course of each other in manifestations, diagnostic and treatment processes. Today, modern science needs to understand the presence of a common genetic origin. It is known that the polymorphic variant of the VDR vitamin D receptor gene has a predisposition to common osteochondral diseases. However, the issue of participation in pathogenetic mechanisms of development and progression remains controversial. A polymorphic variant of the VDR gene has a predisposition to osteochondral diseases. However, its involvement in the pathogenetic mechanisms of the development and progression of osteoarthritis remains controversial, therefore The aim of the study is to investigate the specifics of the impact of comorbid pathology on carbohydrate and lipid metabolism and the state of the vascular wall in patients with osteoarthritis, taking into account the polymorphic variant of the VDR gene (Bsml, rs1544410). Object and research methods. 100 patients were examined and also divided into groups: 1st group – patients with OA; II – OA with arterial hypertension; ІІІ – OA, arterial hypertension (AG) and type 2 diabetes mellitus, a blood sample was taken and, depending on age, comorbidity, the presence of the polymorphic variant BsmI (rs1544410) of the VDR gene, indicators of carbohydrate and lipid metabolism, the level of end metabolites of nitric oxide and endothelin-1 were studied and the impact on radiological changes and the functional state of the knee joints was evaluated. Control – 30 people. Results of the study and their discussion. It has been established that osteoarthritis is characteristic of persons of working age. With increasing age, it is characteristic to be burdened by comorbid pathologies with worsening of the course of the main disease. Expected violation of carbohydrate metabolism was observed in the III group of patients, although dynamic probable changes were also in the II group (p<0.05). Lipid metabolism in the I group was probably higher than the group of control, but was within the physiological norm, while groups II and III had significant pathological changes compared to the indicators of the I group and practically healthy persons. Hypercholesterolemia became a trigger for a decrease in the total level of stable total nitrogen monoxide metabolites and an increase in endothelin-1, which forms endothelial dysfunction and leads to the progression of AG and worsening of the course of OA. After the genotyping and division into genotypes of the polymorphic variant BsmI of the VDR gene, conclusions were obtained about the unfavorable allele A in the exchange processes of the above indicators. Conclusions. Features of violations of carbohydrate and lipid metabolism, the condition of the endothelium, against the background of comorbidity and the presence of an unfavorable allele A of the BsmI polymorphic variant of the VDR gene should be taken into account in the complex diagnostic and treatment process of patients with OA.