Apolipoprotein E and plasminogen activator inhibitor 1 gene polymorphism in children with chronic renal insufficiency associated with cardiovascular disease

Bahia Hassan Moustafa,Nasser Gamal,Ahmed Badr,Abeer Selim,Rania Samy

doi:10.1186/s43054-019-0011-9

Abstract

BackgroundCardiovascular disease (CVD) is considered a major cause of death in renal insufficiency (RI). Contributing genetic factors is a recent focus of research. This study aims to elucidate apolipoprotein E (APO-E) and plasminogen activator inhibitor 1 (PAI-1) gene polymorphisms in RI children associated with CVD.MethodsWe studied 50 cases with chronic kidney disease (CKD) associated with CVD, and 30 healthy controls. Study sample was grouped as one on conservative treatment, the second on hemodialysis and the third was posttransplant. PAI-1 and APO-E gene polymorphisms were investigated using allele-specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively.Results4G4G and 4G5G were the most common PAI-1 polymorphism denoting high association of 4 G allele in renal insufficiency associated with CVD with absent link to dyslipidemia, echocardiography changes or thrombosis. E3E3 was the most common among APO-E polymorphism without relation to dyslipidemia or thrombosis. Dyslipidemia was significantly linked to thrombosis. The study confirmed the role of dyslipidemia and hemodialysis in promoting thrombosis.ConclusionAlthough PAI 4G Genotyping did not show significant association with echocardiography severity or thrombotic severity, yet genetic expression for high levels of PAI in plasma is expected in response to CRI factors known to trigger its release, in addition to those related to dialysis. APO-E3E3 genotyping showed a significant association with echocardiography severity as it enhances APO-A which contributes to CVD. The current study confirmed a significant association between dyslipidemia and CVD; however, the prevalent patterns 4G and E3E3 did not show a significant association with dyslipidemia. The genetic role for APO-A, B, O, or even other isomers for APO-E should be further studied as well.

Highlights

Cardiovascular disease (CVD) is considered a major cause of death in renal insufficiency (RI)
This study investigated the detection of plasminogen activator inhibitor gene and Apolipoprotein E gene polymorphisms by allele-specific PCR (AS-PCR) and Polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) respectively
PAI 4G Genotyping did not show significant association with echocardiography severity or thrombosis severity, yet genetic expression for high levels of PAI in plasma is expected in response to chronic renal insufficiency (CRI) factors known to trigger its release, in addition to those related to dialysis as previously mentioned

Summary

Introduction

Cardiovascular disease (CVD) is considered a major cause of death in renal insufficiency (RI). This study aims to elucidate apolipoprotein E (APO-E) and plasminogen activator inhibitor 1 (PAI-1) gene polymorphisms in RI children associated with CVD. Cardiovascular disease is considered a major cause of death in children with chronic renal failure. Patient gene pattern may contribute to the progress of renal damage as well as the development of accelerated CVD through altering some biochemical and biological processes that are reflected in the kidney and cardiovascular system. PAI-1 levels are related to the rate of renal failure progression after kidney transplantation [7]. A common 4G/5G polymorphism in the promoter region of the human PAI-1 gene has been described and is associated with different levels of serum PAI-1 activity [8]. The 5G variant binds the E2F transcription repressor, whereas 4G fails to do so and is associated with the higher PAI1 plasma level [10]

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