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The citric acid cycle is central to the regulation of energy homeostasis and cell metabolism. Changes of gene expression of enzymes that catalyse steps in the citric acid cycle result in human diseases with various clinical presentations. The malate dehydrogenase 1 (MDH1) gene encodes an enzyme that catalyzes the NAD/NADH-dependent, reversible oxidation of malate to oxaloacetate in many metabolic pathways, including the citric acid cycle. Our previous gene chip study in patients with coronary heart disease (CHD) suggested that MDH1 gene had low expression in the peripheral blood cells. We thought that MDH1 gene may affect the process of the occurrence of CHD. The aim of this study is to determine the expression of MDH1 gene in the peripheral blood cells of patients with CHD, and to analyze its clinical significance.
60 CHD patients were randomly selected and set as the CHD group, and 60 healthy people were selected as the control group. The clinical data of all study subjects including age, gender, diagnosis, blood lipid, blood pressure, blood glucose and medicine treatment were recorded. 2ml of venous blood was sampled from both two groups for RNA extraction; Real-time Quantitative PCR was then performed to detect the expression of MDH1 gene on the transcription level using GAPDH as the internal reference. The relative expression of MDH1 used the 2-ΔΔCt method.
There were no significant differences between these two groups of patients in gender, age, body weight index (BMI), comorbidities, smoking and drinking history. However, there were significant differences in fasting glucose (6.54±2.43 versus 5.74±1.54, P=0.027), total cholesterol (TC) (4.96±1.30 versus 4.42±0.81, P=0.014), triglyceride (TG) (2.30±0.73 versus 1.67±0.89, P=0.018), low-density lipoprotein (LDL) (3.25±0.85 versus 2.80±0.71, P=0.008) and high-density lipoprotein (HDL) (1.04±0.23 versus 1.20±0.35, P=0.040) levels. The CHD group exhibited higher fasting glucose, TC, TG and LDL levels and lower HDL level. At the mRNA level, the relative expression of MDH1 used the 2-ΔΔCt method and the results showed that the expression of MDH1 in the CHD group was lower than the control group, and the relative expression was 0.39±0.11, consistent with the results of our previous microarray assay.
MDH1 gene was down regulated in the peripheral blood cells of CHD patients, and its altered expression might lead to systemic disruption of lipid and glucose metabolism which were risk factors for CHD. This gene may be used as a biomarker for screening risk population of CHD, and the morbidity of CHD could be reduced through early identification and intervention.