Physiological role of PPARG gene Exon 5 variants in evaluating some of the Biomarkers in Dyslipidemia

Abstract

Background: Lipid metabolism disorders (Dyslipidemia) are common metabolic disorders characterized by impaired lipid metabolism and associated with insulin resistance. The peroxisome proliferator-activated receptor gamma (PPARG) gene is responsible for lipid storage and adipocyte differentiation, and also plays a role in glucose metabolism and hormonal regulation. Variations within this gene can lead to loss of gene function and contribute to metabolic disorders.

Objective: The current study aims to evaluate the correlation between hormone levels and physiological markers in individuals with dyslipidemia. Additionally, the study aims to assess the correlation between variants in exon 5 of the PPARG gene and hormonal and physiological markers associated with dyslipidemia.

Method: Thirty individuals with dyslipidemia were selected for this study. Five milliliters of venous blood were drawn from each participant. Three milliliters were used for hormonal and physiological laboratory analyses, and two milliliters were used for molecular analysis of exon 5 of the PPARG gene. Subsequently, computational analysis was performed using bioinformatics algorithms (SIFT, PROVEAN) to predict the functional impact of the variants.

Results: The results of this study indicated a moderate positive correlation between insulin levels and several metabolic markers, including liver enzymes ALT and AST, cholesterol, and triglycerides. A strong correlation was observed with triglycerides. Furthermore, linear regression analysis revealed markers associated with metabolic changes. Genetic analysis identified nonsynonymous mutations within the PPARG gene (Q85R, V142G, Q191H, N47K, and L202P) and predicted their effects on protein function and structure. Furthermore, the correlation between variants and biomarkers was investigated in this study. The results obtained from genetic analysis confirmed that these variants are associated with elevated insulin and leptin levels, as well as elevated triglyceride, cholesterol, and ALT levels. Additionally, the V142G variant showed a strong correlation with metabolic markers, which would reflect the expected effect on protein function, which is linked to PPARG. Regarding hematological variants, the results obtained did not show any correlation with the genetic variants. Conclusion: This suggests that the protein's function is limited to the metabolic pathway and does not extend to hematopoiesis. Therefore, variants within exon 5 of the PPARG gene play a significant role in dyslipidemia, as they affect the normal function of hormones and lipid metabolism.