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Plasminogen Activator Inhibitor-1 Level Associated with the Components of Metabolic Syndrome in a 4G/5G Polymorphism Dependent Manner

Atherosclerosis(2022)

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摘要
Background and Aims : The elevated level of plasminogen activator inhibitor-1 (PAI-1) in obese subjects with metabolic syndrome and in patients with type 2 diabetes is well established. A common 4G/5G single guanine insertion/deletion polymorphism in the promoter region of the PAI-1 gene is of functional importance in regulating PAI-1 expression. We aimed to study the potential different correlations of carbohydrate and lipid parameters and plasma PAI-1 levels in the 4G and 5G carriers in obese and lean subjects.Methods: Ninety-three morbid obese and thirty-two lean non-diabetic participants were enrolled. PAI-1 4G/5G polymorphism was determined with allele-specific PCR. Plasma PAI-1 levels were measured by ELISA.Results: The genotype distribution of PAI-1 4G/5G polymorphism was not significantly differed in obese patients (4G/4G 27.9%; 4G/5G 45.2% and 5G/5G 26.9%) compared to controls (4G/4G 31.3%; 4G/5G 46.9% and 5G/5G 21.9%, p=0.8). Slightly higher PAI-1 levels were found in 4G carriers (4G/4G+4G/5G) in obese and control group (p=0.07 and p=0.02, respectively). In all subjects with 4G/5G genotype, plasma PAI-1 correlated negatively with high-density lipoprotein-cholesterol (HDL-C) (p=0.02) and apolipoprotein AI (apoAI) levels (p<0.001). In 5G/5G participants, PAI-1 also correlated negatively with HDL-C (p=0.025) and apoAI (p=0.007) concentrations, moreover positively with triglyceride (p=0.02), fasting glucose (p=0.002) and haemoglobin A1c (p=0.027). These correlations are lacking in 4G/4G participants.Conclusions: The observed correlations between PAI-1 levels and the components of metabolic syndrome suggest a closer link between PAI-1 and lipid and carbohydrate metabolism in subjects with 5G/5G genotype. This presentation was supported by the Bridging Fund (Faculty of Medicine, University of Debrecen) and PD124126 project. Background and Aims : The elevated level of plasminogen activator inhibitor-1 (PAI-1) in obese subjects with metabolic syndrome and in patients with type 2 diabetes is well established. A common 4G/5G single guanine insertion/deletion polymorphism in the promoter region of the PAI-1 gene is of functional importance in regulating PAI-1 expression. We aimed to study the potential different correlations of carbohydrate and lipid parameters and plasma PAI-1 levels in the 4G and 5G carriers in obese and lean subjects. Methods: Ninety-three morbid obese and thirty-two lean non-diabetic participants were enrolled. PAI-1 4G/5G polymorphism was determined with allele-specific PCR. Plasma PAI-1 levels were measured by ELISA. Results: The genotype distribution of PAI-1 4G/5G polymorphism was not significantly differed in obese patients (4G/4G 27.9%; 4G/5G 45.2% and 5G/5G 26.9%) compared to controls (4G/4G 31.3%; 4G/5G 46.9% and 5G/5G 21.9%, p=0.8). Slightly higher PAI-1 levels were found in 4G carriers (4G/4G+4G/5G) in obese and control group (p=0.07 and p=0.02, respectively). In all subjects with 4G/5G genotype, plasma PAI-1 correlated negatively with high-density lipoprotein-cholesterol (HDL-C) (p=0.02) and apolipoprotein AI (apoAI) levels (p<0.001). In 5G/5G participants, PAI-1 also correlated negatively with HDL-C (p=0.025) and apoAI (p=0.007) concentrations, moreover positively with triglyceride (p=0.02), fasting glucose (p=0.002) and haemoglobin A1c (p=0.027). These correlations are lacking in 4G/4G participants. Conclusions: The observed correlations between PAI-1 levels and the components of metabolic syndrome suggest a closer link between PAI-1 and lipid and carbohydrate metabolism in subjects with 5G/5G genotype. This presentation was supported by the Bridging Fund (Faculty of Medicine, University of Debrecen) and PD124126 project.
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