Endothelial nitric oxide synthase polymorphisms are associated with hypertension and cardiovascular disease in renal transplantation

Abstract

Nitric oxide (NO), produced by the polymorphic endothelial nitric oxide synthase (NOS3), plays an important role in endothelial function. The aim was to determine the effect of NOS3 polymorphisms on hypertension and cardiovascular disease (CVD) in renal allograft recipients. Three polymorphisms of NOS3 were examined in 168 renal allograft recipients. A 27 base pair repeat sequence in intron 4 (NOS3 a/b), a single G-->T substitution in exon 7 at nucleotide 894 and a T-786C substitution in the promoter region were studied. Significant differences in the frequencies of the 894T and -786C alleles between allograft recipients and controls (n = 141) were demonstrated (894T: 40.5% vs 30.1%, P < 0.01; -786C: 45.2% vs 34.4%, P < 0.01). There was a significant excess of both the 894T and -786C alleles in hypertensive allograft recipients compared with normotensive allograft recipients and controls (894T: 41.7%, 35.7% and 30.1%, respectively, P < 0.025; -786C: 47.4%, 37.1% and 34.4%, respectively, P < 0.01), and in allograft recipients with CVD compared with those without CVD and controls (894T: 47.2%, 38.6% and 30.1%, respectively, P < 0.025; -786C: 54.2%, 42.8% and 34.4%, respectively, P < 0.01). The 894T and -786C alleles of the NOS3 gene were significantly associated with both hypertension and CVD in renal allograft recipients.