Tissue factor gene promoter haplotype associates with carotid intima-media thickness in subjects in cardiovascular risk prevention

• Published in: Atherosclerosis Vol. 207; no. 1; pp. 168 - 173
• Main Authors: Gertow, Karl, Amato, Mauro, Werba, José Pablo, Bianchi, Elena, Parolari, Alessandro, Colnago, Deborah, Brambilla, Marta, Ravani, Alessio, Veglia, Fabrizio, Baldassarre, Damiano, Camera, Marina, Tremoli, Elena
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.11.2009; Elsevier
• Subjects: Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cardiovascular Diseases - diagnostic imaging; Cardiovascular Diseases - genetics; Cardiovascular Diseases - prevention & control; Carotid Arteries - diagnostic imaging; Carotid Artery Diseases - complications; Carotid Artery Diseases - diagnostic imaging; Carotid Artery Diseases - genetics; Carotid Artery Diseases - therapy; Carotid intima-media thickness; Coronary heart disease; Female; Gene Frequency; Genetic polymorphism; Genetic Predisposition to Disease; Haplotypes; Heart; Heterozygote; Homozygote; Humans; Linear Models; Male; Medical sciences; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk Assessment; Risk Factors; Secondary Prevention; Thromboplastin - genetics; Thromboplastin - metabolism; Tissue factor; Tunica Intima - diagnostic imaging; Tunica Media - diagnostic imaging; Ultrasonography; CCA; C-IMT; ICA; Tissue factor; HDL; TF; SNP; LDL; Carotid intima-media thickness; Atherosclerosis; Genetic polymorphism; MI; Bif; PCR; tissue factor; high-density lipoprotein; myocardial infarction; carotid intima-media thickness; common carotid artery; low-density lipoprotein; bifurcation; internal carotid artery; single-nucleotide polymorphism; polymerase chain reaction; Human; Cardiovascular disease; Artery; Vascular disease; Prevention; Blood vessel; Carotid; Circulatory system; Haplotype; Polymorphism
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.04.040

Tissue factor (TF), key initiator of coagulation, has been ascribed roles not only in thrombosis but also in atherosclerosis. TF gene promoter haplotypes modulate TF expression, thereby potentially affecting atherosclerosis. The objective of this study was to evaluate functionally relevant TF promoter haplotypes as determinants of carotid intima-media thickness (C-IMT), a marker of atherosclerosis. The haplotype-tagging TF A-603G polymorphism and C-IMT were determined in 611 subjects referred to cardiovascular risk prevention. Subjects were aged 59.7 (58.1–61.1) years (mean (95% C.I.)), 79% were male, and 74% in secondary prevention with a history of coronary, cerebrovascular, or peripheral atherosclerotic disease. TF plasma levels were measured in 120 subjects. Significant dose-dependent associations were found between A-603G genotype and both IMT max and IMT mean-max after adjusting for potential confounders. IMT values were highest in A/A ( n = 173), intermediate in A/G ( n = 312) and lowest in G/G ( n = 126). IMT max values (average and 95% C.I., in mm) for A/A, A/G and G/G, were 2.22 (2.11–2.34), 2.09 (2.01–2.18) and 2.02 (1.90–2.15), respectively ( p trend = 0.019), and IMT mean-max values were 1.28 (1.23–1.32), 1.25 (1.22–1.28) and 1.21 (1.16–1.26), respectively ( p trend = 0.041). A significant interaction between A-603G genotype and prevention status was found ( p = 0.046 and p = 0.042 for IMT max and IMT mean-max, respectively). TF plasma levels did not differ between genotypes and were not determinants of C-IMT. The haplotype-tagging TF A-603G polymorphism is associated with C-IMT, independently of TF levels in plasma. These findings provide clinical evidence of an involvement of TF in atherosclerosis, in addition to its well-known roles in hemostasis and thrombosis.