Endothelial nitric oxide synthase Glu(298)-->Asp polymorphism, carotid atherosclerosis and intima-media thickness in a general population sample.
The Glu(298)-->Asp (E298D; 894G-->T) polymorphism of eNOS (endothelial nitric oxide synthase) has been related with cardiovascular disease. In the present study, we investigated the association of Glu(298)-->Asp with atherosclerotic plaques in different carotid vessel segments and with carotid IMT (intima-media thickness). The Glu(298)-->Asp eNOS polymorphism was determined by 5'-exonuclease assay among 2448 participants of the SHIP (Study of Health in Pomerania). Mean and maximum common carotid IMT, as well as carotid atherosclerosis, were measured by high-resolution ultrasound. The Asp/Asp(298) genotype was associated with an increased risk of atherosclerotic plaques at the level of the common carotid arteries [multivariate odds ratio, 1.57 and 95% CI (confidence interval), 1.05-2.34; P=0.025], but not in the carotid bifurcations or internal or external carotid arteries. Glu(298)-->Asp genotype was not associated with carotid IMT in the whole sample. However, the Asp/Asp(298) genotype was independently associated with both higher mean [adjusted increase by 0.046 mm (95% CI, 0.013-0.078); P=0.006] and maximum carotid IMT [0.137 mm (95% CI, 0.064-0.209); P<0.001] in the low-risk group of subjects without carotid atherosclerosis. In conclusion, the Asp/Asp(298) genotype is associated with atherosclerosis in the common carotid arteries and, in a low-risk group, also with carotid IMT. This suggests that the association of the Glu(298)-->Asp genotype with atherosclerosis in the carotid arteries is site-specific and is modified by overall cardiovascular risk.
Wolff
Birger
B
Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany. birger.wolff@uni-griefswald.de
Braun
Claudia
C
Schlüter
Christina
C
Grabe
Hans J
HJ
Popowski
Katrin
K
Völzke
Henry
H
Lüdemann
Jan
J
John
Ulrich
U
Cascorbi
Ingolf
I
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D002318:Cardiovascular Diseases / Q000209:etiology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014463:Ultrasonography
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III