Atherosclerosis and the Glu298Asp polymorphism of the eNOS gene in white patients with end-stage renal disease.
BACKGROUND
We investigated whether the eNOS G/T polymorphism (Glu298Asp variant) is linked to the severity of carotid atherosclerosis and whether it is independent of asymmetric dimethylarginine (ADMA) in determining vascular damage in patients with end-stage renal disease (ESRD).


METHODS
The eNOS polymorphism, ADMA, carotid intima-media thickness (IMT), and carotid artery (CCA) wall-to-lumen ratio (an indicator of arterial remodeling) were determined/measured in 131 patients with ESRD.


RESULTS
Both in the co-dominant and dominant model approach, IMT as well as CCA wall-to-lumen ratio were directly related to the T allele (P < or = .009) and these relationships held true in multiple linear regression analyses including ADMA and traditional and emerging risk factors. The relationship between eNOS genotypes and CCA wall-to-lumen ratio was further analyzed by a categorical approach and in a multiple logistic regression analysis, the odds ratio (OR) of increased CCA wall-to-lumen ratio was strongly associated to the T allele (codominant model: GG, OR = 1; GT, OR = 2.1; TT, OR = 8.2; P for trend = .01; dominant model: GG, OR = 1; GT and TT, OR = 2.7; P = .02).


CONCLUSIONS
The T allele of eNOS gene is an independent predictor of intimal lesions and vascular remodeling and it is associated with the severity of atherosclerosis independently of ADMA.
Spoto
Belinda
B
CNR-IBIM, National Research Council-Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, 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
Parlongo
Rosa Maria
RM
Pisano
Anna
A
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood / Q000235:genetics / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D044465:White People / Q000235:genetics
C018524:N,N-dimethylarginine; D001120:Arginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III