MArchenko I. Association analysis of the polymorphic variants of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene with the development of type 2 diabetes mellitus and its risk factors

Thesis is dedicated to the study of of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) polymorphic variants impact on the development of type 2 diabetes mellitus (T2DM). The ENPP1 gene (rs997509-, rs1044498-polymorphism) is associated with the development of type 2 diabetes mellitus in the Ukrainian population The influence of ENPP1 gene polymorphic variants on the development of type 2 diabetes mellitus has age-specific features. It was discovered that among people older than 75 years, carriers of the minor T-allele by rs997509-polymorphism, have 4.5 times (OR = 4,561; CI = 1,040–20,014) higher the risk of diabetes than homozygotes for the main C-allele. As a result of our studies, we found that among women with CT-genotype by rs997509 polymorphism the risk of developing diabetes is 3 times higher (P = 0.031; OR = 3.038). Analysis within the dominant model (KQ/QQ vs K/K) of inheritance by rs1044498 polymorphism has also revealed the association of this polymorphic locus with the risk of diabetes in women (P = 0.033; OR = 1.750). Studying the association of gene polymorphic variants of the ENPP1 with the development of type 2 diabetes mellitus and its risk factors, we found out that there is a significant difference in the distribution of genotypes by ENPP1 gene rs997509-polymorphism among obese individuals in diabetes and control groups (Р = 0.024). It was discovered that in obese carriers of the minor T-allele the risk of developing type 2 diabetes is much higher than in homozygotes with the main C-allele (OR = 3.230; P = 0.023). The combination in one individual with a BMI ≥ 25 kg/m2 of the minor T-allele of the 1st intron polymorphism and one of the variants of genotypes K/K, K/Q or Q/Q by the 4th exon polymorphism of the studied gene is a significant predictor of increased risk development of type 2 diabetes.