title: Tissue factor gene promoter haplotype associates with carotid intima-media thickness in subjects in cardiovascular risk prevention.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro Cardiologico Monzino, Via Parea 4, 20138 Milan, Italy. karl.gertow@yahoo.com
authors.forename: Karl
authors.initials: K
authors.lastname: Gertow
authors.forename: Mauro
authors.initials: M
authors.lastname: Amato
authors.forename: José Pablo
authors.initials: JP
authors.lastname: Werba
authors.forename: Elena
authors.initials: E
authors.lastname: Bianchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Parolari
authors.forename: Deborah
authors.initials: D
authors.lastname: Colnago
authors.forename: Marta
authors.initials: M
authors.lastname: Brambilla
authors.forename: Alessio
authors.initials: A
authors.lastname: Ravani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.forename: Damiano
authors.initials: D
authors.lastname: Baldassarre
authors.forename: Marina
authors.initials: M
authors.lastname: Camera
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
mesh_terms: D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography
chemical_list: D013925:Thromboplastin