Significance of the Tumor Necrotic Factor Alpha in Development of Nephropathy in Type 2 Diabetes Mellitus

Abstract

Relevance. The value of tumor necrosis factor alpha (TNFα) and the polymorphism of its gene rs1800629 for the development of type 2 diabetes mellitus (DM) has been shown in some studies but the mechanism of such an effect and role in some ethnic populations of patients is not fully understood.
 Objective: to find out the value of TNFα and polymorphism of its gene rs1800629 in the development of type 2 DM and its vascular complications.
 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 immuneenzyme method (Bender Medsystems, Austria); polymorphism rs1800629 – by real time polymerase chain reaction (TaqMan Mutation Detection Assays Life-Technology, USA). Statistical data processing was used by Statistica 10 (StatSoft, Inc., USA).
 Results. 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 a decrease in the velocity of glomerular filtration and was associated with the development of 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 the 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.

Association between polymorphisms of cytokine genes and diabetic nephropathy: A comprehensive systematic review and meta‐analysis

“…Gupta et al, in north India on 100 DN patients showed that the carriers of −1031T/C were significantly associated with high TNF‐α levels and risk of development of DN 19 . Moreover, Ziablitsev et al study on 152 Ukrainian patients with T2D showed that the presence of the allele A rs1800629 was an important factor in DN development, and Allele A contributed to a decrease in the velocity of glomerular filtration 71 . Consistent with the above mentioned studies, our pooled analyses found a statistically significant association between the C allele vs the T allele (rs1799964) and the risk of DN.…”