The role of polymorphism of candidate genes in the development of knee osteoarthritis in men of the Central Chernozem region of Russia

Abstract

Knee osteoarthritis (OA) is a disease resulting from the interaction of many local and systemic risk factors, among which an important role is played by genetic (hereditary) factors. This disease affects both men and women, but there are certain differences in the development and progression of the disease in different sexes.Aim: To study associations of polymorphic loci of candidate genes with the risk of developing knee ОА in the male population of the Central Chernozem region of Russia.Material and Methods. The study sample included 410 men (208 patients with knee OA and 202 controls). Ten polymorphic loci of candidate genes were genotyped: rs2820436 and rs2820443 LYPLAL1, rs3771501 TGFA, rs11177 GNL3, rs6976 GLT8D1, rs1060105 and rs56116847 SBNO1, rs6499244 NFAT5, rs34195470 WWP2, rs143384 GDF5. The study of associations of polymorphic genetic loci with the development of the disease was carried out by the method of logistic regression, taking into account covariates (age, BMI). The MB-MDR method was used to study intergenic interactions of polymorphisms associated with the disease.Results and Discussion. It was found that nine out of ten polymorphic loci of candidate genes (with the exception of rs6976 GLT8D1) are associated with the formation of knee OA in men in four models of interlocus interactions (pperm ≤ 0.024). The rs3771501 TGFA polymorphic locus (included in three of the four most significant models of gene-gene interactions) demonstrates the greatest contribution to the development of the disease in men. Independent effects of the studied polymorphic loci of candidate genes in the development of knee OA in men have not been identified (р > 0,05).Conclusion. Polymorphic loci rs2820436 and rs2820443 LYPLAL1, rs3771501 TGFA, rs11177 GNL3, rs6976 GLT8D1, rs1060105 and rs56116847 SBNO1, rs6499244 NFAT5, rs34195470 WWP2, rs143384 GDF5 involved in the development of knee osteoarthritis in men in four models of intergenic interactions. Among the studied loci, rs3771501 of the TGFA gene has the greatest contribution to disease susceptibility.