title: 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.
abstract: 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.
authors.affiliation: 2nd Department of Cardiology, Athens University, Athens, Greece. lekakis@tellas.gr
authors.forename: John P
authors.initials: JP
authors.lastname: Lekakis
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.forename: Maria
authors.initials: M
authors.lastname: Tsibida
authors.forename: Athanasios
authors.initials: A
authors.lastname: Protogerou
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Papada
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Papapanagiotou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Revela
authors.forename: Christos M
authors.initials: CM
authors.lastname: Papamichael
authors.forename: Anastasios T
authors.initials: AT
authors.lastname: Kalofoutis
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: 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
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III