Contribution of rs11927381 polymorphism of the IGF2BP2 gene to the pathogenesis of type 2 diabetes
Background: Pancreatic beta-cell dysfunction, along with the insulin resistance of peripheral tissues, is a key element in the pathogenesis of type 2 diabetes (T2D). In this regard, of considerable interest is the study of the role of polymorphisms of the genes directly involved in the work of the beta cells of the islets of Langerhans in the formation of susceptibility to the disease. The aim of the study: To study the relationship of the polymorphic variant of the gene encoding insulin like growth factor 2 mRNA binding protein 2, IGF2BP2, (T>C, rs11927381) with the risk of developing T2D in the residents of the Kursk region. Materials and methods: The study included 559 patients with type 2 diabetes and 540 healthy volunteers. Genotyping of the IGF2BP2 gene polymorphism (T>C, rs11927381) was performed using iPLEX technology on a genomic time-of-flight mass spectrometer MassArray Analyzer 4 (Agena Bioscience). Statistical analysis was performed with the use of the online program SNPStats. Results: The frequency of the C/C genotype was significantly higher in the group of patients with T2D compared with the control group (OR 1.75; 95% CI 1.25-2.44; P=0.0026). The association retained its significance after adjustment for sex, age and body mass index (OR 1.87; 95% CI 1.26-2.78; P=0.0054). A gender-stratified analysis showed that the identified association was typical only for men (OR 2.27; 95% CI 1.17-4.40; P=0.041), while in women it was not observed (P>0.05). C/T and C/C genotypes were associated with a decrease in total cholesterol and low-density lipoproteins in patients with T2D (P<0.05). Conclusion: The established association indicates the involvement of the IGF2BP2 gene in the formation of susceptibility to T2D. The studied variant of rs11927381 is also associated with lower levels of total cholesterol and low-density lipoproteins in type 2 diabetic patients that may account for the SNP effects on epigenetic markers, such as methylation and acetylation.