Traumatology and Orthopedics of RussiaTraumatology and Orthopedics of Russia2311-29052542-0933Vreden National Medical Research Center of Traumatology and Orthopedics197910.17816/2311-2905-1979Research ArticlePolymorphism of LYPLAL1 and TGFA Genes Associated With Progression of Knee Osteoarthritis in Residents Central Chernozem Region of RussiaNovakovVitaly B.v.novakov@bk.ruhttps://orcid.org/0000-0001-5337-2156NovakovaOlga N.<p>Cand. Sci. (Biol.)</p>litovkina@bsu.edu.ruhttps://orcid.org/0000-0003-2700-1284ChurnosovMikhail I.<p>Dr. Sci. (Med.), Professor</p>churnosov@bsu.edu.ruhttps://orcid.org/0000-0003-1254-6134Belgorod National Research UniversityCity Hospital No. 22612202228442530408202214102022Copyright © 2022, Eco-Vector2022<p><strong><em>Background.</em></strong> 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.</p>
<p><strong><em>The study aimed</em></strong> to evaluate the role of polymorphic markers of candidate genes rs2820436 and rs2820443 <em>LYPLAL1</em>, rs3771501 <em>TGFA</em>, rs11177 <em>GNL3</em>, rs6976 <em>GLT8D1</em> in the progression of knee OA in the population of the Central Chernozem Region of Russia.</p>
<p><strong><em>Methods.</em></strong> 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.</p>
<p><strong><em>Results.</em></strong> Significant associations with the progression of OA of the knee were established for allelic variant A rs2820436 of <em>LYPLAL1</em> gene according to allelic (OR = 1.48, p = 0.010, p<sub>perm</sub> = 0.012), additive (OR = 1.58, p = 0.009, p<sub>perm </sub>= 0.010), dominant (OR = 1.61, p = 0.024, p<sub>perm</sub> = 0.030) genetic models and A/A genotype of the same polymorphism (OR = 2.53, p = 0.041). The genotypes C/C rs2820436 <em>LYPLAL1</em> (OR = 0.67, p = 0.043), A/G rs3771501 <em>TGFA</em> (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, p<sub>perm</sub> = 0.002). The identified molecular genetic markers rs2820436 and rs2820443 of <em>LYPLAL1</em> gene, rs3771501 of <em>TGFA</em> 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.</p>
<p><strong><em>Conclusions.</em></strong> Genetic risk factors for the development of knee OA of III-IV radiological stages are allelic variant A and genotype A/A rs2820436 of <em>LYPLAL1</em> gene, haplotype AC of haploblock rs2820436-rs2820443 in the population of the Central Chernozem Region of Russia. Genotypes C/C rs2820436 of <em>LYPLAL1</em> gene and A/G rs3771501 of <em>TGFA</em> gene have a protective value in the progression of this disease.</p>knee osteoarthritisLYPLAL1TGFApolymorphic locusassociationscandidate genesостеоартроз коленного суставаLYPLAL1TGFAполиморфный локусассоциациигены-кандидаты[Reynard L.N., Barter M.J. Osteoarthritis year in review 2019: genetics, genomics and epigenetics. Osteoarthritis Cartilage. 2020;28(3):275-284. doi: 10.1016/j.joca.2019.11.010.][Katz J.N., Arant K.R., Loeser R.F. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA. 2021;325(6):568-578. doi: 10.1001/jama.2020.22171.][Alekseeva L.I., Taskina E.A., Kashevarova N.G. 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