Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus

Fatma A Khalaf,Waseem M Gaber,Maha M Allam,Samia T Ali,Hatem R Ibrahim,Amr A Elshormilisy,Hanan M Bedair

doi:10.1186/s43042-019-0018-1

Abstract

BackgroundDiabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications. Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Several studies have revealed definitive genetic predispositions to the development of type 2 diabetes mellitus (T2DM) and development of vascular complications. This study aimed to address the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and T2DM, and if this gene polymorphism may have a possible role in the development of vascular complications in T2DM. This study is a case control; it included 200 patients with T2DM, 117 patients had no vascular complications, and 83 had previous vascular complications (VCs). One hundred eighty volunteer blood donors were selected as a healthy control group. All patients and controls were subjected to clinical examination, and laboratory investigations included lipid profile, fasting and 2 h blood glucose, complete blood cell count, d-dimer, PAI-1, thrombin activatable fibrinolysis inhibitor (TAFI), and detection of PAI-1 gene polymorphism by real-time polymerase chain reaction (PCR).ResultsThe most prevalent genotype of PAI-1 gene polymorphism in all studied groups, including controls, was 4G/5G with the highest allele frequency as 4G. The 4G/5G and 4G/4G genotypes were associated with increased risk of DM development as compared to 5G/5G genotype. The 4G/5G and 4G/4G genotypes also had a highly significant increased risk of VCs among diabetic patients, as compared to 5G/5G. The 4G allele also was highly associated with DM with VCs. The d-dimer TAFI, PAI-1 showed the highest levels in 4G/5G genotype followed by 4G/4G genotype. The lowest level was expressed in 5G/5G genotype in diabetic patients with and without VCs. The univariable analysis showed that genotypes 4G/5G and 4G/4G were potentially risk factors for development of VCs with T2DM patients.ConclusionThis study concludes that the PAI-1 4G/5G polymorphism may be associated with T2DM and may be considered as a risk factor for development of thrombotic events. It may also help in selection and dosing of patients being treated with anticoagulant and fibrinolytic agents. Further large-scale studies are recommended to assess the possible role of environmental factors and gene interactions in the development of T2DM vascular risks.

Highlights

Diabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications
Diagnosis of diabetes was performed according to American Diabetes Association (ADA) 2018, with either fasting blood glucose greater than 126 mg/dl, 2–h post-prandial blood sugar greater than 200 mg/dl during oral glucose tolerance test (OGTT), or hemoglobin A1C (HbA1C) greater than 6.5%
The mean levels of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood sugar (FBS), 2-hr 2-Hours post brandial sugar (PBS), hemoglobin A1C (HbA1c %), total cholesterol, and low-density lipoprotein (LDL) among the studied groups were significantly higher in diabetic patients compared to control group, but were not significantly different between both patient groups

Summary

Introduction

Diabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Type 2 diabetes mellitus (T2DM) is a common metabolic disease in developing countries, in which combined insulin resistance and beta-cell impairment lead to hyperglycemia [1]. Most of the complications caused by hyperglycemia involve damage to small vessels which leads to neuropathy, nephropathy and retinopathy, and large blood vessels, as in cardiovascular diseases. Risk factors such as hypertension, dyslipidemia, and obesity can increase the risk of type 2 DM. Insulin resistance and hyperglycemia are associated with low-grade inflammation as well as chronic enhancement of oxidative stress, triggering endothelial dysfunction and promoting atherogenesis [4]

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