Abstract
BackgroundIncreased oxidative stress or an impaired antioxidant defense mechanism may play a crucial role in the onset and progression of atherosclerosis. Recently, Paraoxonase −1 (PON1) which accounts for most of the antioxidant effect of high density lipoprotein (HDL) cholesterol has been presented as a potential therapeutic agent against atherosclerosis development. Allele frequencies for PON1 gene that influence enzyme concentration as well as activity differ greatly among ethnic groups and data from several studies showed ethnic variations in the interpretation of cardiovascular disease (CVD) associated with PON1 polymorphisms. In this work, we investigated PON1 Q192R and L55M polymorphisms in Egyptian patients with type 2 diabetes mellitus (T2DM) and its association with CVD.MethodsThe study included 184 subjects classified into 3 groups; T2DM, T2DM + CVD, and healthy controls. PON1 polymorphisms were genotyped by real-time PCR and PON1 concentration was assayed in serum by ELISA (enzyme linked immunesorbent assay).ResultsGenotype and allele frequencies of Q192R were significantly different between controls and diabetic patients. Frequency of QQ genotype was significantly higher in healthy controls, while QR and RR genotypes were significantly higher in diabetic patients (p = 0.02). Frequency of 55LL and LM genotypes were significantly higher in patients than in controls (p = 0.009). Q192R polymorphism associated with CVD in our diabetic patients (p = 0.01) and with low serum PON1 concentration (p = 0.04). Multiple logistic regression analysis revealed significant correlations between 192R and other independent CVD risk factors.ConclusionPON1 192R and 55 L alleles are associated with T2DM. Q192R polymorphism is associated with CVD and lower serum enzyme concentration and might represents a novel risk factor for CVD in Egyptian patients with T2DM.
Highlights
Diabetes mellitus (DM) is a chronic life-threatening disease and is the second leading cause of death worldwide with at least 1 in 10 deaths among adults between 35 and 64 years old is attributable to diabetes [1]
Our study included 184 subjects classified into 68 patients with type 2 diabetes mellitus (T2DM), 66 patients with T2DM+cardiovascular disease (CVD), and 50 control subjects
Other clinical data such as BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in both groups when compared to controls
Summary
Diabetes mellitus (DM) is a chronic life-threatening disease and is the second leading cause of death worldwide with at least 1 in 10 deaths among adults between 35 and 64 years old is attributable to diabetes [1]. Cardiovascular disease (CVD) is the most common cause of morbidity and mortality among diabetic patients. PON1 is a 355 amino acid glycoprotein which is synthesized in the liver and secreted into the blood where it associates with HDL and accounts for most of its antioxidant effect to prevent oxidation of LDL [6,7]. Increased oxidative stress or an impaired antioxidant defense mechanism may play a crucial role in the onset. Increased oxidative stress or an impaired antioxidant defense mechanism may play a crucial role in the onset and progression of atherosclerosis. Paraoxonase −1 (PON1) which accounts for most of the antioxidant effect of high density lipoprotein (HDL) cholesterol has been presented as a potential therapeutic agent against atherosclerosis development. We investigated PON1 Q192R and L55M polymorphisms in Egyptian patients with type 2 diabetes mellitus (T2DM) and its association with CVD
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