Association of plasminogen activator inhibitor-1 4G/4G genotype and type 2diabetic nephropathy in Chinese patients

Background Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of fibrinolytic pathway and extracellular matrix (ECM) turnover. Because diabe tic nephropathy is characterized by the presence of basement membrane thick ening and mesangial expansion, we examined the role of PAI-1 gene polymorph isms in the development of type 2 diabetic nephropathy. Evidence also sugge sted that the PA/plasmin system and the renin-angiotensin system (RAS) inte ract together to affect the risk of fibrosis and thrombosis. Hence, we also studied the synergistic effect between PAI-1 and angiotensin-converting en zyme (ACE) gene polymorphisms. Methods. The PAI-1 and ACE (D/I) gene polymorphisms were examined in a coho rt of Chinese type 2 diabetic patients who had diabetes for an average of 1 4 years. These patients were sex and age matched. Group A (N = 46) consiste d of patients without diabetic nephropathy (normoalbuminuric with creatinin e <120 mu mol/L), and group B (N = 95) was with diabetic nephropathy (with albuminuria or renal impairment, including patients on dialysis). Results. Patients with type 2 diabetic nephropathy had a higher frequency o f PAI-1 (4G/4G) genotypes than those without nephropathy [4G/4G:4G/5G:5G/5G = 41:38:21 (%) vs. 15:65:20(%), P = 0.005]. Diabetic patients with coexist ence of PAI-1 4C/4G genotype and ACE D alleles had a higher incidence of di abetic nephropathy (22 vs. 7 %, P = 0.012) than those with other combinatio ns of genotypes. Multivariate logistic regression analysis showed that PAI- 1 4G/4G (P = 0.01) and the prevalence of hypertension (P < 0.0001) are inde pendent risk factors of development of type 2 diabetic nephropathy. Conclusions. These results suggest that the PAI-1 4G/4G genotype is associa ted with an increased risk for type 2 diabetic nephropathy in Chinese patie nts, which is an independent risk factor for the development of nephropathy . The PAI-1 4G/4G genotype also exhibits a synergistic effect with the ACE D allele on development of diabetic nephropathy.