Analysis of the association of FTO, PPARG and PPARGC1A gene polymorphisms with carbohydrate metabolism disorders

Abstract

Background. Conducting molecular and genetic studies to investigate susceptibility to multifactorial and polygenic diseases, such as type 2 diabetes melitus and pre-diabetic conditions, is of great importance for the development of personalized prevention programs and the choice of optimal treatment. Taking into account regional and ethnic features, the study of polymorphic markers of candidate genes for fat and carbohydrate metabolism has a great practical value. Aim. To investigate associations of polymorphisms of the FTO rs9939609, PPARG rs180128, PPARGC1A rs8192678 genes with the risk of developing type 2 diabetes mellitus and pre-diabetic conditions in residents of the Republic of Tatarstan. Material and methods. An observational single-stage single-center controlled study was conducted in patients with various disorders of carbohydrate metabolism: prediabetes (n=138) and a confirmed diagnosis of type 2 diabetes mellitus (n=134). Molecular genetic analysis of rs9939609 polymorphism of the FTO gene, rs8192678 polymorphism of the PPARGC1A gene and rs1801282 polymorphism of the PPARG gene was performed using real-time polymerase chain reaction. The distribution of patient genotypes and alleles was compared with the Russian population. Statistical data processing included nonparametric correlation analysis using Pearsons coefficient, calculation of Student's and 2 tests, odds ratios, arithmetic mean values and their standard deviations using GraphPad InStat software. Results. The A allele of the rs9939609 polymorphism of FTO gene increases the risk of developing type 2 diabetes mellitus and early carbohydrate metabolism disorders (OR=2.73, p=0.00007 and OR=4.17; p=0.00002, respectively). The GG genotype of the rs180128 polymorphism of the PPARG gene is associated with the risk of type 2 diabetes mellitus (OR=2.77, p=0.02). Conclusion. The expected association of the rs9939609 FTO polymorphic marker, which determines the development of insulin resistance, with the development of type 2 diabetes mellitus and the presence of early carbohydrate metabolism disorders was obtained.