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

Abstract

Background: 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. 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). Results: The 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. Conclusion: This 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.

Association between polymorphism in BMP15 and GDF9 genes and impairing female fecundity in diabetes type 2

“…According to the duration of the disease, the genotypic frequency did not exhibit significant differences among T2DM (Table 5). In agreement with this result, Khalaf et al [64] found no significant differences were observed between the PAI-1 genotypes and the diabetes duration.…”

Quality of glycemic control in type 2 diabetes mellitus (T2DM) and its association with markers of coagulation and inhibitors of fibrinolysis: A case–control study in the Upper West Region, Ghana

“…On the contrary, Nkansah et al 17 in their study recorded a significantly higher plasma level of PAI-1 antigen and activity in T2DM patients than controls, and this disparity could be due to genetic variations between our study groups as other genetic studies indicated that polymorphisms in PAI-1 gene (genetic variants) influence the plasma levels of the antigen. 27,28 The probable explanation for our study finding could also imply that the medications used in the management of T2DM patients may have beneficial impacts in limiting the plasma levels of antifibrinolytics. In our present study, a majority of T2DM individuals were on metformin treatment-a biguanide known to reduce the plasma levels of PAI-1.…”

Plasminogen activator inhibitor 1 and gestational diabetes: the causal relationship

“…Furthermore, polymorphism of PAI-1 is linked with the development of dyslipidemia [ 34 ]. Notably, polymorphism of PAI-1 increases the risk for the development of cardiovascular complications in patients with T2DM [ 35 ]. Herein, a high PAI-1 level in GDM may counterbalance the development of cardio-metabolic complications.…”