Genome-wide studies of knee osteoarthritis (review)

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Introduction. Knee Osteoarthritis (OA) is a multifactorial disease resulting from the interaction of many environmental, epigenetic and genetic risk factors, and the latter account for 40% to 65%. Genetic bases of the knee OA based on genome-wide association search (GWAS) are being actively studied by many scientific teams around the world. At the same time, the results obtained are often contradictory and ambiguous, as for the conducted replicative studies of knee OA. This dictates the need for additional replicative studies in various populations, including populations of Russia, which are characterized by significant ethno-territorial variability, in order to identify specific GWAS-significant polymorphic markers of candidate genes associated with OA in these individual populations. The aim of the study was to analyze genome-wide studies of knee OA and to establish GWAS-significant polymorphic loci associated with OA. Materials and methods. The search for publications was carried out in the electronic databases PubMed, PubMedCentral, eLIBRARY, in the GWAS catalog for the period from 2008 to the present by the keywords: knee osteoarthritis, GWAS studies, candidate genes. Results. First, to date, 14 genome-wide studies of knee OA have been performed, as a result of which about 80 GWAS-significant polymorphic loci associated with the risk of knee OA have been identified. Secondly, all GWAS of the knee OA were carried out abroad on samples from various foreign populations, and the samples from the Russian Federation were not included in these studies. Third, only two GWAS-significant polymorphic loci for OA (rs143384 of the GDF5 gene and rs3771501 of the TGFA gene) were replicated at the genome-wide significance level (p≤5x10-08) in two different studies. Fourth, the data obtained indicate the presence of two regions of chromosomes (6p21.32 and 7q22.3), in which the largest number of GWAS-significant polymorphic loci for OA is located - 3SNPs in each (6p21.32 - rs10947262, rs7775228, rs9277552; 7q22.3 - rs4730250, rs10953541, rs3815148). Fifth, with an increase in the volume of the studied samples of patients and control in genome-wide studies of knee OA, the number of identified GWAS-significant polymorphisms also increases. Conclusion. The main genome-wide studies of knee OA were reviewed and GWAS-significant polymorphisms associated with OA were identified. The obtained materials on GWAS-significant loci can be used both in the selection of polymorphisms in replicative studies of OA in various populations of Russia, and for expanding the understanding of the molecular genetic mechanisms of the disease development.

About the authors

Vitaly B. Novakov

City Hospital №2 of Belgorod, Belgorod, Russia;
Belgorod National Research University, Belgorod, Russia

ORCID iD: 0000-0001-5337-2156
Orthopaedic Surgeon, City Hospital №2 of Belgorod, Belgorod, Russia;
PhD Student, Belgorod National Research University, Belgorod, Russia
Russian Federation

Olga N. Novakova

Belgorod National Research University, Belgorod, Russia

Author for correspondence.
ORCID iD: 0000-0003-2700-1284
Cand. Sci. (Biol.), Associate Professor of the Department of Biomedical Disciplines of the Medical Institute, Belgorod National Research University, Belgorod, Russia Russian Federation

Mikhail I. Churnosov

Belgorod National Research University, Belgorod, Russia

ORCID iD: 0000-0003-1254-6134
Dr. Sci. (Med.), Professor, Head of the Department of Medical and Biological Disciplines of the Medical Institute, Belgorod National Research University, Belgorod, Russiа Russian Federation


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Copyright (c) Novakov V.B., Novakova O.N., Churnosov M.I.

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