Genetic markers of knee osteoarthritis in women of the Central Chernozem region of Russia
Background: Knee osteoarthritis (KO) is a multifactorial disease. Among the many risk factors for the disease, the role of the hereditary component is undeniable. The share of genetic factors in the development of OA is about 50%. The aim of the study: To study the role of polymorphic loci of candidate genes in the development of knee osteoarthritis in women from the Central Chernozem region of Russia. Materials and methods: The sample for the study included 590 women, including 292 patients diagnosed with KO and 298 women in the control group. All study participants underwent genotyping of four polymorphic loci of candidate genes (rs2820443 LYPLAL1, rs11177 GNL3, rs56116847 SBNO1 and rs34195470 WWP2), which showed an association with KO in previous genome-wide studies. A logistic regression analysis was carried out (allelic, additive, recessive, dominant genetic models were tested), taking into account covariates (age, BMI, hereditary burden, the presence of diseases of the cardiovascular, endocrine, musculoskeletal systems). Results: The minor allele A rs11177 of the GNL3 gene was found to be associated with the development of KO in women according to allelic (OR=0.74, pperm=0.011), additive (OR=0.65, pperm=0.009), dominant (OR=0.58, рperm=0.025) and recessive (OR=0.56, рperm=0.042) genetic models. The GG genotype rs11177 of the GNL3 gene is a risk factor for the development of KO (OR=1.53, p=0.026). The identified associations of rs11177 of the GNL3 gene with the development of the disease in females may be associated with the pronounced functional effects of this SNP: it determines the missense mutation (Arg39Gln in the GNL3 polypeptide); it is localized in an evolutionarily conservative region, in the area of hypersensitivity to DNase-1, in the area of histones, marking promoters in 10 tissues and enhancers in 14 tissues, in the region of binding to the regulatory protein ZNF263 and in the region of the regulatory DNA motif – RXRA; it is associated with the level of expression of 24 genes and alternative splicing of 12 genes in various tissues and organs involved in the pathogenesis of KO (adipose tissue, thyroid gland, skeletal muscles, etc.). Conclusion: The A allelic rs11177 variant of the GNL3 gene has a protective role in the development of KO in women of the Central Chernozem Region of Russia (OR=0.56-0.74), the GG genotype rs11177 has a risk role for the disease (OR=1.53).
Novakov VB, Novakova ON, Sorokina IN, et al. Genetic markers of knee osteoarthritis in women of the Central Chernozem region of Russia. Research Results in Biomedicine. 2023;9(2): 191-205. Russian. DOI: 10.18413/2658-6533-2023-9-2-0-4
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