The GLU298ASP variant of nitric oxide synthase interacts with asymmetric dimethyl arginine in determining cardiovascular mortality in patients with end-stage renal disease.

TY - JOUR

T1 - The GLU298ASP variant of nitric oxide synthase interacts with asymmetric dimethyl arginine in determining cardiovascular mortality in patients with end-stage renal disease.

AU - Testa, Alessandra

AU - Spoto, Belinda

AU - Tripepi, Giovanni

AU - Mallamaci, Francesca

AU - Malatino, Lorenzo

AU - Fatuzzo, Pasquale

AU - Maas, Renke

AU - Boeger, Rainer

AU - Zoccali, Carmine

PY - 2005

Y1 - 2005

N2 - OBJECTIVES: Impaired nitric oxide generation and accumulation of the endogenous inhibitor of nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), have been identified as strong predictors of cardiovascular outcomes in patients with end-stage renal disease (ESRD). We evaluated the role of endothelial NOS (eNOS) gene polymorphisms and its interaction with plasma ADMA in the high cardiovascular complications rate of these patients. METHODS: The relationship between the Glu298Asp variant of eNOS and all-cause and cardiovascular mortality was assessed in a cohort study including 261 ESRD patients that were followed up for an average of 42 months. RESULTS: During the follow-up period, 138 patients died, 81 of them (i.e. 59% of total deaths) of cardiovascular causes. On univariate Cox's regression analysis, eNOS genotype tended to be related to all-cause death but failed to reach formal statistical significance (P for trend=0.11). However, eNOS genotype showed a significant association with cardiovascular mortality in statistical models, including traditional risk factors and factors peculiar to ESRD, and became even stronger when plasma ADMA was forced into the Cox model (P=0.006). Furthermore, the risk of cardiovascular death was maximum in heterozygotes and homozygotes patients carrying the risk allele and in those having high ADMA levels (hazard ratio=2.71, 95% confidence interval 1.38-5.35, P=0.004) compared to those having just one of these two risk factors. CONCLUSIONS: The T allele of the Glu298Asp polymorphism predicts cardiovascular mortality and interacts with plasma ADMA in determining this outcome in dialysis patients.

AB - OBJECTIVES: Impaired nitric oxide generation and accumulation of the endogenous inhibitor of nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), have been identified as strong predictors of cardiovascular outcomes in patients with end-stage renal disease (ESRD). We evaluated the role of endothelial NOS (eNOS) gene polymorphisms and its interaction with plasma ADMA in the high cardiovascular complications rate of these patients. METHODS: The relationship between the Glu298Asp variant of eNOS and all-cause and cardiovascular mortality was assessed in a cohort study including 261 ESRD patients that were followed up for an average of 42 months. RESULTS: During the follow-up period, 138 patients died, 81 of them (i.e. 59% of total deaths) of cardiovascular causes. On univariate Cox's regression analysis, eNOS genotype tended to be related to all-cause death but failed to reach formal statistical significance (P for trend=0.11). However, eNOS genotype showed a significant association with cardiovascular mortality in statistical models, including traditional risk factors and factors peculiar to ESRD, and became even stronger when plasma ADMA was forced into the Cox model (P=0.006). Furthermore, the risk of cardiovascular death was maximum in heterozygotes and homozygotes patients carrying the risk allele and in those having high ADMA levels (hazard ratio=2.71, 95% confidence interval 1.38-5.35, P=0.004) compared to those having just one of these two risk factors. CONCLUSIONS: The T allele of the Glu298Asp polymorphism predicts cardiovascular mortality and interacts with plasma ADMA in determining this outcome in dialysis patients.

M3 - SCORING: Zeitschriftenaufsatz

VL - 23

SP - 1825

EP - 1830

JO - J HYPERTENS

JF - J HYPERTENS

SN - 0263-6352

IS - 10

M1 - 10

ER -