The rs1800629 polymorphism of the TNFα gene in type 2 diabetes mellitus: association with nephropathy

• Main Authors: S.V. Ziablytsev, O.P. Chernobrytsev, D.S. Ziablytsev
• Format: Article
• Language: English
• Published: Publishing House Zaslavsky 2019-02-01
• Series: Mìžnarodnij Endokrinologìčnij Žurnal
• Subjects: type 2 diabetes mellitus; nephropathy; endothelial dysfunction; rs1800629 polymorphism of TNFα gene
• Online Access: http://iej.zaslavsky.com.ua/article/view/158687
• ISSN: 2224-0721; 2307-1427

Background. In diabetes mellitus (DM), endothelial dysfunction (EDF) is formed that determines the rate and severity of the disease complications. Among other factors, there is the presence of genetic polymorphism, which can be different in different ethnic populations. The purpose was to determine the relationship between rs1800629 polymorphism of the TNFα gene and type 2 DM in Ukrainian patients, as well as the association with the development of complications and EDF factors. 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 apparently healthy persons (controls). According to the results of clinical and laboratory examinations, the presence of retinopathy, nephropathy was determined by levels of microalbuminuria and glomerular filtration rate, sensory polyneuropathy, angiopathy of the lower extremities, and hypertension. The rs1800629 polymorphism was determined by real time polymerase chain reaction (Gene Amp® PCR System 7500 Applied Biosystems, USA) using the TaqMan Mutation Detection Assays Life­Technology (USA) test systems. Statistical data processing was performed by Statistica 10 (StatSoft Inc., USA). Results. The distribution of alleles (χ2 = 5.91; p = 0.015), but not genotypes (χ2 = 5.65; p = 0.059) rs1800629 of the TNFα gene was associated with the disease development in the Ukrainian cohort of patients with type 2 DM. Minor allele A increased the risk of type 2 DM (odds ratio = 1.71; 95% confidence interval 1.11–2.65). The presence of allele A led to the reduction of glomerular filtration rate that explained the association of rs1800629 with nephropathy (χ2 = 6.38; p = 0.041) and was due to the development of EDF with high levels of TNFα (p < 0.001), endothelin­1 (p = 0.026) and nitric oxide (p < 0.001). Conclusions. The rs1800629 polymorphism of the TNFα gene was associated with the type 2 DM in patients from the Ukrainian population, and among the complications — with the development of nephropathy in terms of the glomerular filtration rate, which was related to the presence of minor allele A and more severe EDF in such patients as compared to G allele carriers.