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Thromb Haemost 2006; 96(04): 520-528
DOI: 10.1160/TH06-05-0280
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

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

John P. Lekakis
1   2nd Department of Cardiology, Athens University, Athens, Greece
,
Ignatios Ikonomidis
1   2nd Department of Cardiology, Athens University, Athens, Greece
,
Maria Tsibida
2   Department of Biological Chemistry, Athens University, Athens, Greece
,
Athanasios Protogerou
3   Department of Clinical Therapeutics, Alexandra University Hospital, Athens, Greece
,
Aggeliki Papada
2   Department of Biological Chemistry, Athens University, Athens, Greece
,
Aggeliki Papapanagiotou
2   Department of Biological Chemistry, Athens University, Athens, Greece
,
Ioanna Revela
3   Department of Clinical Therapeutics, Alexandra University Hospital, Athens, Greece
,
Christos M. Papamichael
3   Department of Clinical Therapeutics, Alexandra University Hospital, Athens, Greece
,
Anastasios T. Kalofoutis
2   Department of Biological Chemistry, Athens University, Athens, Greece
,
Dimitrios T. Kremastinos
1   2nd Department of Cardiology, Athens University, Athens, Greece
› Author Affiliations
Further Information

Publication History

Received 19 May 2006

Accepted after resubmission 21 July 2006

Publication Date:
29 November 2017 (online)

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Summary

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 with T-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 for VNTR), 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.

Keywords

NO synthase gene polymorphisms - inflammation - atherosclerosis - vascular function
 

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