Polymorphisms of the methylenetetrahydrofolate reductase, vascular endothelial growth factor, endothelial nitric oxide synthase, monocyte chemoattractant protein-1 and apolipoprotein E genes are not associated with carotid intima-media thickness.
BACKGROUND
Single nucleotide polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), monocyte chemoattractant protein-1 (MCP-1) and apolipoprotein E (ApoE) genes appear to be a genetic risk factor for atherosclerosis. Common carotid intima-media thickness (cIMT) provides information on the severity of atherosclerosis.


OBJECTIVE
To investigate the relationship between cIMT and gene polymorphisms associated with atherosclerosis in Turkish patients with coronary artery disease (CAD).


METHODS
Sixty-two patients with angiographically diagnosed stable CAD were divided into two groups according to their cIMT values (group 1: n=35, cIMT of 1 mm or greater; group 2: n=27, cIMT of less than 1 mm). MTHFR 677 C/T, VEGF --460 C/T, eNOS 894 G/T, MCP-1 --2518 A/G and ApoE (E2, E3 and E4) gene polymorphisms (where A is adenine, C is cytosine, G is guanine and T is thymine) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Evaluations of cardiovascular risk factors and coronary atherosclerotic lesions were performed in all patients. Serum homocysteine and high-sensitivity C-reactive protein were measured and compared between the two groups.


RESULTS
Serum high-sensitivity C-reactive protein (P=0.04) and homocysteine (P=0.006) levels were higher in group 1 than in group 2. The ratio of multivessel CAD and previous myocardial infarction was significantly higher in group 1 than in group 2 (P=0.014). In the study population, no significant difference in cIMT was observed according to the polymorphisms studied. Only hyperhomocysteinemia (OR 1.17 [95% CI 1.01 to 1.35], P=0.033) and previous myocardial infarction (OR 3.76 [95% CI 1.10 to 12.81], P=0.034) maintained a significant correlation with cIMT on multiple logistic regression analysis.


CONCLUSIONS
cIMT is increased in patients with hyperhomocysteinemia, inflammation and extended CAD. MTHFR 677 C/T, VEGF --460 C/T, eNOS 894 G/T, MCP-1 --2518 A/G and ApoE single nucleotide polymorphisms were not associated with increased cIMT.
Alioglu
Emin
E
Department of Cardiology, Central Hospital, Bayrakli, Izmir, Turkey. dreminalioglu@yahoo.com
Turk
Ugur
U
Cam
Sirri
S
Abbasaliyev
Abbasali
A
Tengiz
Istemihan
I
Ercan
Ertugrul
E
D001057:Apolipoproteins E / Q000235:genetics*; D002097:C-Reactive Protein / Q000032:analysis; D017536:Carotid Artery, Common / Q000473:pathology*; D018932:Chemokine CCL2 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D001057:Apolipoproteins E; D018932:Chemokine CCL2; D042461:Vascular Endothelial Growth Factor A; D006710:Homocysteine; D002097:C-Reactive Protein; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2)