Sobha Santhi Priya, Sankar Jeyanthi, Muthusamy Karthikeyan, Kesavarao Kumar Ebenezar
Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, 603103, India.
Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, Tamil Nadu, 630003, India.
Biochem Genet. 2024 May 27. doi: 10.1007/s10528-024-10823-4.
The genetic alteration in the antioxidant gene Glutathione-S-Transferases Pi 1 (GSTP1) namely GSTP1IIe105Val (rs1695) and GSTP1Ala114Val (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.
抗氧化基因谷胱甘肽 - S - 转移酶Pi 1（GSTP1）中的基因改变，即GSTP1IIe105Val（rs1695）和GSTP1Ala114Val（rs1138272），通过改变底物结合和催化活性，改变了个体对心血管疾病（CVD）和2型糖尿病（T2DM）的易感性。本研究旨在探讨GSTP1 rs1695和rs1138272多态性与T2DM患者CVD发生之间的关联。采用聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）方法对400名研究参与者进行基因分型，分为四组：第一组为对照组；第二组为T2DM组；第三组为CVD组；第四组为T2DM/CVD组[每组n = 100]。将rs1695和rs1138272多态性与NPACT和NUBBE数据库进行对接，并使用Glide进行虚拟筛选。研究报告称，在显性和等位基因遗传模型下，rs1695多态性与T2DM风险相关[OR分别为1.97(1.08 - 3.59)，p = 0.02和OR为1.79(1.20 - 2.66)，p = 0.003]。val/val基因型、显性、隐性模型以及T等位基因遗传模型与CVD风险增加相关[OR分别为4.15(1.97 - 8.73)，p < 0.01；OR为3.16(1.65 - 6.04)，p < 0.01；OR为3.47(1.91 - 6.31)，p < 0.01；OR为2.94(1.95 - 4.43)，p < 0.01]。相比之下，rs1695多态性与T2DM患者的CVD发生无关。在rs1138272中，仅检测到野生基因型，未观察到杂合子或val/val基因型。对接分析显示，与Ala115Val突变相比，Ile105Val突变在改变GSTP1能力方面起重要作用。这表明与Ala115Val突变相比，Ile105Val突变对蛋白质的结构、功能或疾病易感性有更大影响。总之，GSTP1 rs1695中的基因改变可能导致T2DM和CVD风险增加。
