Genetic variations of the endothelial nitric oxide synthase gene are related to increased levels of C-reactive protein and macrophage-colony stimulating-factor in patients with coronary artery disease.
It was the objective of this study to investigate the relation between nitric oxide synthase (NOS3) gene polymorphisms, vascular inflammation, endothelial function, and atherosclerosis. We examined the effects of a variable nucleotide tandem repeats (VNTR) in intron 4, G894T in exon 7 and T-786C at the promoter region of NOS3 on i) C-reactive protein (CRP) and macrophage-colony stimulating-factor (MCSF), and ii) augmentation index (AI) measured by pulse-wave analysis , flow-mediated dilation (FMD) of the brachial artery, intima-media thickness (IMT) of the carotid and femoral artery using ultrasonography and ankle-brachial index (ABI) in 122 patients with chronic coronary artery disease (CAD) who underwent coronary angiography. MCSF and CRP were increased in patients withT-786C (77/122) or VNTR (40/122) allele compared to those without (F = 10.8, p = 0.002 and F = 3.8, p = 0.04 for T-786C and F = 3.65, p = 0.04 and F = 3.2 p = 0.049 forVNTR), even after adjustment for traditional risk factors and medication. Patients with combination of VNTR and T-786C (31/122) had higher MCSF or CRP than patients with one or none of these alleles (p < 0.05). Among patients with T-786C, those with MCSF>262 pg/ml or CRP>3.2 mg/l (n = 33/77) had a higher femoral and carotid IMT and number of plaques in the peripheral arteries than those with lower values of these inflammatory indices (p < 0.05). Patients with MCSF >262 pg/ml had also lower FMD and higher Gensini score than those with lower MCSF (p < 0.05). The intron 4-VNTR and T-786C mutation of NOS3 gene enhance the inflammatory process in patients with chronic CAD.
Lekakis
John P
JP
2nd Department of Cardiology, Athens University, Athens, Greece. lekakis@tellas.gr
Ikonomidis
Ignatios
I
Tsibida
Maria
M
Protogerou
Athanasios
A
Papada
Aggeliki
A
Papapanagiotou
Aggeliki
A
Revela
Ioanna
I
Papamichael
Christos M
CM
Kalofoutis
Anastasios T
AT
Kremastinos
Dimitrios T
DT
D002097:C-Reactive Protein / Q000378:metabolism*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D005091:Exons; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007438:Introns; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D016173:Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III