Significance of the tumor necrotic factor alpha in mechanisms of nephropathy development in type 2 diabetes mellitus

Abstract

The value of tumor necrosis factor alpha (TNFα) and the polymorphism of its gene rs1800629 for develop­ment of type 2 diabetes mellitus (DM) has been shown in some stu­­dies but the mechanism of this effect and its role in some ethnic populations of patients is not fully understood. Objective — to determine the value of TNFα and the polymorphism of its gene rs1800629 in mecha­nisms of vascular complications development in type 2 diabetes. Materials and methods. The study involved data from 152 Ukrainian patients with type 2 DM, aged 34—80 years (53.9 ± 8.4 years) and 95 healthy persons (control). According to the results of clinical and la­­boratory examinations, the presence of complications was determined and the stage of the disease was established. The blood level of TNFα was determined by the immunoenzyme method (Bender Medsystems, Austria); polymorphism rs1800629 — by real time polymerase chain reaction (TaqMan Mutation De­­tection Assays Life-Technology, USA). Statistical data processing was performed by Statistica 10 (StatSoft, Inc., USA). Results and discussion. The blood level of TNFα in type 2 DM significantly increased in accordance with the severity of the disease (the maximum in the third stage — 7.1 times; p = 3.2e-17), which influenced the development of retinopathy (β = 0.012; p = 0.049), nephropathy by glomerular filt­ration rate (β = 0.011; p = 0.007) and arterial hypertension (β = 0.007; p = 0.042); the maximum was the effect on the development of macroan­giopathy of the lower extremities (β = 0.033; p < 0.001). Minor allele A rs1800629 increased (OR = 1.71; 95 % CI 1.11-2.65; p = 0.015) risk of type 2 DM. For genotypes the connec­tion with the disease is confirmed by the dominant model of inheritance (G/G versus G/A+A/A; OR = 1.87; 95 % CI 1.10-3.18; p = 0.020). Allele A contributed to decrease ofglomerular filtration rate and was associated with nephropathy (χ2 = 6.38; p = 0.041). This could be due to higher TNFα levels in G/A genoty­pes-carriers (1.2 times) and A/A (1.7 fold) compared to genotype G/G-carriers (p < 0.001). Conclusion. The presence of allele A rs1800629 was an important factor in the diabetic nephropathy development; one of the mechanisms of the vascular diabetic complications development was excessive expression of the TNFα gene, resulting in excessive synthesis of TNFα.