Effect of IL4-589C>T, FCGR2A-166His>Arg, DEFB1-20G>A, DEFB1-52G>A gene polymorphisms on TNFα, IL-1β, IL-4, and IL-10 contents in the patients with primary hip osteoarthrosis

Abstract

Our objective was to study the effects of IL4-589C>T, FCGR2A-166His>Arg, DEFB1-20G>A, DEFB1-52G>A gene polymorphisms upon content of TNFα, IL-1β, IL-4, and IL-10 in primary osteoarthrosis of the hip joints. We performed a survey of 100 patients of Russian ethnicity (average age 61.3±8.5 years) with primary coxarthrosis at the stage III-IV who lived in the Trans-Baikal region. The control group (n = 100), were local residents, comparable by age (60±8.3 years), gender, habitation place and nationality. The exclusion criteria were as follows: close relationship; other types of osteoarthritis (post-traumatic, rheumatoid, metabolic, etc.); dysplastic syndromes and phenotypes; acute and chronic inflammatory diseases at the exacerbation stage; diabetes mellitus; osteoporosis; vascular diseases; obesity; malignant neoplasia; alcohol abuse. Along with clinical examination, the following laboratory methods were applied: immunological techniques, i.e., determination of TNFα, IL-1β, IL-4, IL-10; genetic testing using polymerase chain reaction, e.g., a point mutation of the IL4 gene at the 589(C>T) position, FCGR2A at 166(His>Arg) site, DEFB1 at the 20(G>A) and 52(G>A) positions. DNA from the peripheral blood of patients was used for the molecular genetic analysis. Radiographic examination was also carried out. The data were statistically processed using STATISTICA 6.1 software package (StatSoft, USA), Microsoft Office Excel 2019 for Windows 10. The differences were considered statistically significant at p ≤ 0.05. Results. The -589T/T genotype of IL4-589C>T gene polymorphism indirectly contributes to higher content of TNFα and IL-1β for primary osteoarthritis of the hip joints. The patients with -166Arg/Arg genotype have a 1.3-fold increase of certain cytokine concentrations, e.g., TNFα and IL-1β, as compared with -166His/Arg genotype, and, conversely, lower content of IL-4 and IL-10 (1.3- fold) in comparison with -166His/His genotype. The patients with -20A/A genotype showed higher levels of TNFα and IL-1β, respectively, 1.2 and 1.3 times, compared with -20G/G genotype, and 1.3 times versus the -20G/A genotype. Conclusions: 1. The presence of -589T/T genotype of the IL4-589C>T gene polymorphism and the -20A/A genotype of the DEFB1-20G>A gene polymorphism contributes to a high content of TNFα and IL-1β in the blood serum, and the carriage of -166His/His FCGR2A-166His>Arg gene polymorphism is associated with both higher level of TNFα, IL-1β, and a low concentration of IL-4, IL-10. 2. Complex carriers of FCGR2A166HisArg x DEFB152AA x DEFB120AA x IL4589TT genotypes in the patients with primary coxarthrosis increases the contents of TNFα, IL-1β cytokines by 1.5 and 1.7 times, respectively.

Keywords

• polymorphism
• genes
• cytokines
• primary osteoarthrosis
• hip joints