The contribution of aminopeptidase gene polymorphism and environmental risk factors to the determination of predisposition to type 2 diabetes mellitus

Abstract

Background. One of the known mechanisms of development and progression of type 2 diabetes mellitus (T2D) is oxidative stress. As an enzyme of glutathione metabolism, aminopeptidase ANPEP plays an important role in the body’s antioxidant system.
Aim: to analyze the contribution of polymorphisms of the ANPEP gene and environmental risk factors to the formation of predisposition to T2D.
Methods. The study included genomic DNA samples obtained from 1579 T2D patients and 1627 healthy volunteers. Genotyping was performed using MALDI-TOF mass spectrometry (MassARRAY Analyzer 4, Agena Bioscience) and real-time PCR (CFX 1000, Bio-Rad). Statistical processing of the obtained data was carried out using the online programs SNPStats, PLINK, MBMDR.
Results. A protective effect of the combination of carriage of the rs12148357, rs25653 and rs11073891 polymorphisms of the ANPEP gene and the absence of smoking and psycho-emotional stress, consumption of normal amounts of fats, carbohydrates, fiber and fresh plant foods was established. At the same time, rs9920421 and rs7111 are associated with an increased risk of developing T2D only in combination with a high-calorie diet and protein deficiency in food. A total of 5165 significant two-locus models of gene-environment interactions associated with the risk of developing T2D were identified (84.8% of the models were SNPs and 15.2% were environmental factors).
Conclusion. Environmental factors modulate the risk of developing T2D in carriers of ANPEP gene polymorphisms. At the same time, polymorphic variants of ANPEP and other genes regulating redox homeostasis closely interact with T2D candidate genes and environmental factors in determining the risk of developing T2D.