Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic...

Area of Science:

• Nephrology
• Cardiology
• Genetics

Background:

• Chronic kidney disease (CKD) accelerates cardiovascular disease and heart failure.
• The eNOS Glu298Asp polymorphism is linked to worse outcomes in heart failure and renal disease progression.
• This study investigates the cardiac function in non-dialysis CKD patients without prior heart failure in relation to this gene variant.

Purpose of the Study:

• To investigate the association between the eNOS Glu298Asp single nucleotide polymorphism (SNP) and cardiac function in non-dialysis CKD patients.
• To identify potential genetic biomarkers for sub-clinical cardiac remodeling in CKD.
• To explore pathways for intervention in CKD patients at risk of cardiac disease.

Main Methods:

• Retrospective genotyping of 140 non-dialysis CKD patients for the eNOS Glu298Asp SNP.
• Utilizing cardiac magnetic resonance (CMR) imaging and tissue Doppler echocardiography data from clinical trials.
• Analyzing associations between genotypes and cardiac parameters, adjusting for multiple clinical factors.

Main Results:

• No significant diastolic dysfunction was observed in the cohort (median eGFR 50 ml/min, LVEF 74%).
• The GG genotype of eNOS Glu298Asp was associated with significantly worse left ventricular ejection fraction (LVEF) compared to other genotypes (p=0.006).
• Multivariate analysis confirmed GG genotype was linked to worse LVEF and increased LV end-diastolic and systolic indices (p=0.004, 0.049, 0.009 respectively).

Conclusions:

• The eNOS Glu298Asp rs1799983 polymorphism is associated with sub-clinical cardiac remodeling in CKD patients, detectable by CMR.
• This gene variant may serve as a crucial genetic biomarker for predicting cardiac disease progression in CKD.
• Identifying this biomarker could highlight potential therapeutic targets for intervention in high-risk CKD populations.