Association of endothelial nitric oxide synthase gene intron 4 polymorphism with end-stage renal disease


Dr Maria H Bellini, Instituto de Pesquisas Energéticas e Nucleares, Cidade Universitária IPEN-CNEN/SP, Avenue. Lineu Prestes, 2242, 05508-900, São Paulo, SP, Brazil. Email:


Background:  Nitric oxide (NO) released from endothelial cells is related to the maintenance of physiological vascular tone. The impairment of endothelial NO generation brought about by gene polymorphism is considered one of the deterioration factors in progressive renal disease. In the endothelial nitric oxide synthase (eNOS) intron 4 polymorphism, the presence of the aa genotype has been associated with cardiovascular and renal disease. The aim of this study was to investigate the presence of eNOS gene intron 4 polymorphism in patients with end-stage renal disease (ESRD).

Methods:  A total of 114 patients and 94 controls were studied. DNA specimens were extracted from blood and amplified by polymerase chain reaction. The alleles were separated by agarose gel electrophoresis. Genotype distribution and allele frequencies were compared between groups using the chi-squared test.

Results:  Statistical analysis revealed that the frequency of the eNOS4 genotype aa was significantly different in ESRD patients and in controls (P = 0.016, OR = 2.07, CI 95%: 1.14–3.74). There was also a statistically significant difference between ESRD patients and controls regarding allele carriers (P = 0.004; OR = 2.26; CI 95%: 1.29–3.96). When the frequencies of allele carriers in the diabetic nephropathy group and in the control group were compared, a significant difference was found (P = 0.034, OR = 2.28; CI 95%: 1.04–5.00).

Conclusion:  This study showed a strong correlation between eNOS4a polymorphism and end-stage renal disease.