Risk of Cardiovascular Complications Among Type 2 Diabetes Mellitus Patients with GSTP1 Genetic Polymorphism: A Nested Case-Control Study and Docking Studies.

Abstract

The genetic alteration in the antioxidant gene Glutathione-S-Transferases Pi 1 (GSTP1) namely GSTP1*IIe105Val (rs1695) and GSTP1*Ala114Val (rs1138272) changes the individual susceptibility to cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) by altering the substrate binding and catalytic activity. This study aims to investigate the association of GSTP1 rs1695 and rs1138272 polymorphism with CVD development in T2DM patients. Genotyping was performed with 400 study participants-group I: control; group II: T2DM; group III: CVD; and group IV: T2DM/CVD [n = 100 each] by PCR-RFLP. The rs1695 and rs1138272 polymorphism were docked against NPACT and NUBBE database and virtually screened using glide. The study reported that rs1695 polymorphism was associated with T2DM risk under dominant and allelic genetic models [OR = 1.97(1.08-3.59) p = 0.02 and OR = 1.79(1.20-2.66) p = 0.003, respectively]. The val/val genotype, dominant, recessive model, and T allelic genetic model were associated with increased CVD risk [OR = 4.15(1.97-8.73) p = < 0.01; OR = 3.16(1.65-6.04) p = < 0.01; OR = 3.47(1.91-6.31) p = < 0.01; and OR = 2.94(1.95-4.43) p = < 0.01, respectively]. In contrast, rs1695 polymorphism was not associated with CVD development among patients with T2DM. In rs1138272, the wild genotype was only detected and neither heterozygous nor val/val genotype was observed. The docking analysis revealed that the Ile105Val mutation plays a significant role in altering the GSTP1 capacity compared to the Ala115Val mutation. This suggests that the Ile105Val mutation has a greater impact on the protein's structure, function, or susceptibility to diseases compared to the Ala115Val mutation. In summary, genetic alteration in GSTP1 rs1695 potentially contributes to an increased risk of T2DM and CVD.