The Role of Angiotensin-Converting Enzyme (ACE) Polymorphisms in the Risk of Development and Treatment of Diabetic Nephropathy

Author:

Król-Kulikowska Magdalena1ORCID,Abramenko Nikita23ORCID,Jakubek Milan23ORCID,Banasik Mirosław4ORCID,Kepinska Marta1ORCID

Affiliation:

1. Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland

2. BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic

3. Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, 120 00 Prague, Czech Republic

4. Department and Clinic of Nephrology and Transplantation Medicine, Faculty of Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland

Abstract

Background: Angiotensin-converting enzyme (ACE) is responsible for the production of angiotensin II, and increased production of angiotensin II is observed in diabetes. What is more, ACE polymorphisms may play a role in the development of diabetic nephropathy. The aim of this study was to assess the role of selected ACE polymorphisms (rs4343 and rs4646994) in the risk of development of diabetic nephropathy and in the likelihood of renal replacement therapy. Methods: ACE polymorphisms were analyzed in a group of 225 patients who were divided into three subgroups. The rs4343 polymorphism was determined using the PCR-RFLP, and the rs4646994 polymorphism was determined using the PCR. Molecular docking between domains of ACE and its ligands was performed by using AutoDock Vina. Results: The G/G genotype of rs4343 polymorphism is associated with increased odds of developing diabetic nephropathy. The G allele is also associated with a higher risk of this disease. Similar results were obtained in patients who had already had a kidney transplant as a result of diabetic nephropathy. Conclusions: The presence of G/G and G/A genotypes, and the G allele increases the likelihood of developing diabetic nephropathy. This may also be a risk factor for renal replacement therapy.

Funder

Wroclaw Medical University

Publisher

MDPI AG

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