Association of plasminogen activator inhibitor-1 gene polymorphism and type 2 diabetic nephropathy

Abstract

Background: We investigated the relationship between plasminogen activator inhibitor-1 (PAI-1) 4G/5G insertion/deletion polymorphism and prevalence of diabetic nephropathy (DN) in Chinese patients. Methods: A total of 107 patients with type 2 diabetes were randomly recruited in the study, and 102 healthy subjects were selected as Control. Patients were divided into three groups according to their urinary albumin-creatinine ratio (UACR). Group A (n ¼ 44), had patients without DN (serum creatinine 5106 mmol/L and UACR 530 mg/mg); Group B (n ¼ 30), had patients with micro-albuminuria (UACR 30-299 mg/mg), and Group C (n ¼ 33), had patients with macro-albuminuria (UACR !300 mg/mg and creatinine5200 mmol/L). Plasma level of PAI-1 was measured by ELISA. PAI-1 polymorphism was determined by a polymerase chain reaction (PCR) method and DNA sequencing. Results: (1) The plasma PAI-1 levels of group A (60.39 ± 17.01 ng/L), group B (68.76 ± 17.81 ng/L) and group C and (68.63 ± 18.30 ng/L) are higher than that of controls (46.26 ± 26.04 ng/L); (2) Patients with genotype 4G/4G tended to exhibit higher PAI-1 level; (3) The distribution frequency of genotype 4G/4G in group C was significantly higher than in group A (42.4% vs. 28.7%, p50.05) and (4) In type 2 diabetic patients, the occurrence of diabetes nephropathy in genotype 4G/4G, 4G/5G and 5G/5G is 35.0%, 30.2% and 21.4%, respectively. Conclusions: (1) Plasma PAI-1 level was elevated in Type 2 diabetic patients; (2) The level of plasma PAI-1 is closely related to PAI-1 gene 4G/5G polymorphism and (3) PAI-1 4G/5G polymorphism is associated with the development and progression of predominant proteinuria diabetes nephropathy.

Associations of serum anti-ganglioside antibodies and inflammatory markers in diabetic peripheral neuropathy

“…An increase of PAI-1 volume in plasma would lead to the reduction of fibrinolytic activity and hypercoagulability of the body [30], causing occlusion of vascular stenosis and occurrence of ischemic area in the blood wall. Xu et al revealed that PAI-1 levels were elevated in patients with type 2 diabetic nephropathy [31]. Additionally, our study also examined associations between inflammatory markers and clinical parameters in DPN patients, and revealed that PAI-1, TNF-a, and CRP levels were related to duration of disease, diabetic foot populations, HbA1c, FBG, TC, and TG in DPN patients.…”

Role of plasminogen activator inhibitor‑1 in the diagnosis and prognosis of patients with Parkinson's disease

“…Plasminogen activator inhibitor-1 (PAI-1) serves an important role in the process of human cardiovascular diseases, which thereby leads to promotion of fibrinolysis (8,9). Xu et al (10) have recently demonstrated that PAI-1 gene polymorphism is associated with the development and progression of predominant proteinuria diabetes nephropathy. In addition, high plasma levels of thrombomodulin, PAI-1 and fibrinogen were detected in elderly, diabetic patients with depressive symptoms and further prospective larger studies are required to provide potential directions for future research, treatment and prevention of co-morbid depression and diabetes (8).…”

Influence of Plasminogen Activator Inhibitor -1 Gene Polymorphism on Renal Scarring After First Febrile Urinary Tract Infection in Infants

“…RPD occurs only in part of the children’s population because of serious inflammation. It is certain that PAI-1 genotype may be a predictor of progression of chronic renal disease ( 21 , 22 , 23 ). Study of Roelofs and colleagues in experimental animals (mice) had shown that PAI-1 is critically involved in host defense against Escherichia coli, modeled neutrophils influx and thus stimulates APN ( 24 ).…”