An additive effect of endothelial nitric oxide synthase gene polymorphisms contributes to the severity of atherosclerosis in patients on dialysis.
BACKGROUND
Reduced synthesis of nitric oxide (NO) is considered a major proatherogenic mechanism in patients with end-stage renal disease (ESRD), but genetic factors impinging on this mechanism have been little studied in this population.


METHODS
We tested the relationship between carotid intima-media thickness (IMT) and three endothelial NO synthase (eNOS) polymorphisms (G894T, T-786C, and 27-bp repeat in intron 4) in an ethnically and geographically homogeneous group of 147 patients with ESRD.


RESULTS
The IMT was significantly thicker (P = .01) in patients with the TT genotype (G894T polymorphism) than in patients with TG or GG genotypes, and a similar association was observed for the T-786C polymorphism (P = .02). These relationships remained statistically significant (P = .02 and .01), also in multivariate models including traditional and emerging risk factors for atherosclerosis. Moreover, there was a direct association between the number of risk alleles and IMT (no risk allele: 0.97 +/- 0.22 mm, 1 risk allele: 1.03 +/- 0.20 mm, 2 risk alleles: 1.07 +/- 0.22 mm, > or =3 risk alleles: 1.23 +/- 0.36 mm, P < .001) that remained statistically significant in a multiple regression model.


CONCLUSIONS
In patients on dialysis the risk alleles of G894T and T-786C polymorphisms of the eNOS gene are associated with carotid atherosclerosis. The additive effect of the two polymorphisms may contribute to the severity of atherosclerosis independently of other risk factors and of endogenous substances that influence the NO synthesis in this population.
Spoto
Belinda
B
CNR-IBIM, Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension & Division of Nephrology, Reggio Calabria, Italy.
Benedetto
Francesco A
FA
Testa
Alessandra
A
Tripepi
Giovanni
G
Mallamaci
Francesca
F
Maas
Renke
R
Boeger
Rainer H
RH
Zoccali
Carmine
C
D000328:Adult; D000368:Aged; D000483:Alleles; D050197:Atherosclerosis / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007558:Italy; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D006435:Renal Dialysis; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D052250:Nitric Oxide Synthase Type III