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 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.