Importance of PGC-1α gene expression in Egyptian hemodialysis patients

Abstract

IntroductionThe peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is an upstream transcriptional regulator of mitochondrial biogenesis and function. Its function is immediate elimination of reactive oxygen species to get rid of their cellular destruction sequelae. Decreased PGC-1α count and less mitochondrial function take part in renal failure. COX6C gene encodes mitochondrial oxidative phosphorylation proteins. Reaction of excessive reactive oxygen species with linolenic acid results in malondialdehyde (MDA) as a breakdown product. It is an important marker for evaluating oxidative damage.Patients and methodsA total of 58 hemodialysis (HD) patients in the National Institute of Urology and Nephrology and 20 apparently healthy participants as controls were enrolled in the study. PGC-1α and COX6C gene expressions were assessed by quantitative real-time PCR. Plasma MDA was assayed by ELISA. We followed up patients for 50 months for cardiovascular disease (CVD) and mortality.ResultsPGC-1α expression level was insignificantly downregulated (P = 0.07), COX6C gene expression level was significantly downregulated (P < 0.001), and plasma MDA level was significantly higher (P < 0.001) in HD patients than in controls. There was a significant negative association between PGC-1α expression and MDA in both HD patient and control groups (r=−0.73 and r=−0.76, respectively; P ≤ 0.001 for both). We also found in patients who developed HD-related CVD, lower PGC-1α gene expression (P < 0.001), lower COX6C gene expression (P < 0.001), and higher plasma MDA level (P < 0.001) when compared with HD patients without CVD. By multivariate regression analysis, we found that PGC-1α gene expression was an independent predictor factor (P < 0.001) of CVD development.ConclusionPGC-1α could be a risk factor for occurrence of HD-linked CVD. Pharmacological modification of PGC-1α protein activity might be a hopeful therapeutic way to minimize oxidative stress-related clinical complications in HD patients.