Abstract

Objectives. Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays a key role in the transendothelial migration of circulating leukocytes during inflammation and in the maintenance of vascular endothelial integrity. We hypothesized that genetic variation in PECAM-1 gene could be associated with diabetic nephropathy (DN) and with the level of soluble PECAM-1 in Caucasians with type 2 diabetes mellitus (T2DM). Design and Methods. We analyzed the rs688 single nucleotide polymorphism of PECAM-1 gene C373G (Leu125Val) at exon 3, which encodes the first extracellular Ig-like domain that mediates the homophilic binding of PECAM-1, in 276 T2DM subjects with documented DN (cases) and 375 T2DM subjects without DN (controls), using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy. Level of plasma soluble PECAM-1 (sPECAM-1) was measured by ELISA in a subpopulation of 120 diabetics with DN. Results. We found no association between the Leu125Val polymorphism and DN in subjects with T2DM. Likewise, the Leu125Val polymorphism was not associated with serum sPECAM-1 levels in a subpopulation of 120 diabetics with DN. Conclusion. The Leu125Val polymorphism of PECAM-1 and the level of sPECAM-1 are not associated with DN in T2DM subjects of Slovenian origin.

Highlights

  • Diabetic nephropathy (DN) is the leading cause of endstage renal disease and a major risk factor for cardiovascular disease [1, 2]

  • There were no significant differences between groups with respect to age, sex, duration of type 2 diabetes mellitus (T2DM), diastolic blood pressure, body mass index (BMI), smoking status, family history of cardiovascular disease (CVD), duration of diabetic retinopathy (DR), estimated glomerular filtration rate, serum hemoglobin (Hb), total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) cholesterol levels

  • In the present case-control study that included 651 Caucasian subjects with T2DM, we failed to confirm an association between the rs688 single nucleotide polymorphism of Platelet endothelial cell adhesion molecule-1 (PECAM-1) gene (Leu125Val) and DN

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Summary

Introduction

Diabetic nephropathy (DN) is the leading cause of endstage renal disease and a major risk factor for cardiovascular disease [1, 2]. Patients with DN have a higher risk of mortality, mainly due to cardiovascular complications, in comparison with diabetic patients without nephropathy [2]. As the number of patients with type 2 diabetes mellitus (T2DM) with end-stage renal disease has increased significantly over the past two decades, more research is required to discover new approaches to prevent or slow this worsening of renal function. Inflammation is characterized by leukocyte infiltration at every stage of renal involvement and by increased expression of adhesion molecules, chemokines, and proinflammatory cytokines [1]. Increased levels of cell adhesion molecules in T2DM were shown to be strongly associated with both DN and cardiovascular disease complications and mortality [4]

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