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

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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. Genoty** 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.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors acknowledge Chettinad Academy of Research and Education, Kelambakkam, India, for providing the infrastructure facilities to carry out the work and Dr. Govindaraju Soundararajan for his assistance and support in data analysis with statistics. We would also like to acknowledge Indian Council of Medical Research (ICMR), New Delhi, India for the funding in the form of Senior Research Fellowship (SRF).

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The authors declare that no funds or grants were received during the preparation of this manuscript.

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Author notes

  1. Kumar Ebenezar Kesavarao

    Present address: College of Allied Health Sciences, SRM Institute of Science and Technology, Irungalur, Trichy, Tamil Nadu, 621105, India

Authors and Affiliations

  1. Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, 603103, India

    Santhi Priya Sobha & Kumar Ebenezar Kesavarao

  2. Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, Tamil Nadu, 630003, India

    Jeyanthi Sankar & Karthikeyan Muthusamy

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Contributions

All authors contributed to the study conception and design. Methodology, manuscript writing—original draft, investigation, and data curation were performed by Santhi Priya S; Bioinformatics investigation, bioinformatics writing—manuscript were performed by Jeyanthi Sankar and Karthikeyan Muthusamy; Writing review and editing were performed by Kumar Ebenezar K and Karthikeyan Muthusamy. All authors read and approved the final manuscript.

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Correspondence to Kumar Ebenezar Kesavarao.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Human Ethics Committee (IHEC), Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Kelambakkam-603103, Chengalpattu Dt., TN, India (Date: 05/12/2019; IHEC No: 611/IHEC/11-19).

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Sobha, S.P., Sankar, J., Muthusamy, K. et al. Risk of Cardiovascular Complications Among Type 2 Diabetes Mellitus Patients with GSTP1 Genetic Polymorphism: A Nested Case–Control Study and Docking Studies. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10823-4

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