Peroxisome proliferate activator receptor-γ (PPAR-γ) gene expression and global DNA methylation as predictors for insulin resistance in healthy adults

Year 2025, Volume: 29 Issue: 1, 272 - 279

Sara Haider Khalid Zainab Hassan Hashim Qasim Sharhan Al-mayah

Abstract

Finding a feasible test for screening for insulin resistance (IR) in healthy adults can significantly reduce the
incidence of plethora of metabolic and cardiovascular diseases and for this reason the current study was aimed to
evaluate the prognostic value of peroxisome proliferator-activated receptor γ (PPAR-γ) gene expression and global DNA
methylation in prediction of IR in healthy adults in a cross-sectional study conducted on 100 euglycemic, non-diabetic
apparently healthy adults of both sexes, aged ≥45 years old with HbA1C ≤6.5%, who were categorized into insulin
sensitive (IS) and IR according to Homeostatic Model Assessment of IR (HOMA-IR). Global DNA methylation was
estimated with enzyme linked immune-sorbent assay using a ready commercial kit. Quantitative polymerase chain
reaction (qPCR) was used to estimate PPAR-γ gene expression in relation reference gene and the results revealed that
out of 100 apparently healthy subjects, 30 subjects (30%) had IR. The ∆Ct of PPARγ gene was significantly lower in the IR
individuals (6.49±2.46) in comparison to 8.13±1.37 of the IS individuals. However, it has relative low sensitivity and
specificity (56% and 53%, respectively). There was no significant difference between individual with and without IR in
the intensity of global DNA methylation that may lead to conclude that PPAR-γ gene expression is significantly reduced
in individuals with IR; however, it cannot be used as a screening test for IR, due to low sensitivity and specificity. Global
DNA methylation seems to have no association with IR.

Keywords

Global DNA methylation, homeostatic model assessment, insulin resistance, peroxisome proliferate activator receptor-γ gene, type 2 diabetes

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