Coagulation factor XII (FXII) plays a key role in both coagulation and fibrinolysis and has been associated with cardiovascular disease in some studies. Plasma FXIIa levels are strongly determined by a common functional polymorphism in the promoter of the FXII gene (F12-4C>T). To investigate the potential association of this polymorphism with peripheral arterial disease (PAD), we performed a case-control study including 668 patients with PAD and 762 controls participants without cardiovascular disease. F12 genotype frequencies were not significantly different between patients with PAD and control participants. After adjustment for classical risk factors, the odds ratio of carriers of a F12 -4T allele for PAD was 1.06 (95% confidence interval 0.86—1.32). F12 genotypes were associated with a modest increase of the mean-activated partial thromboplastin time but not with PAD stage or severity. We conclude that the functional F124C>T polymorphism is not associated with PAD.
Gordon EM, Hellerstein HK, Ratnoff OD, Arafah BM, Yamashita TSAugmented Hageman factor and prolactin titers, enhanced cold activation of factor VII and spontaneous shortening of prothrombin time in survivors of myocardial infarction. J Lab Clin Med. 1987 ;109(4): 409-413.
4.
Kohler HP, Carter AM, Stickland MH, Grant PJLevels of activated FXII in survivors of myocardial infarction- association with circulating risk factors and extent of coronary artery disease. Thromb Haemost. 1998;79(1):14-18.
5.
Zito F., Drummond F., Bujac SR, et al. Epidemiologic and genetic associations of activated factor XII concentration with factor VII activity, fibrin generation, and risk of coronary heart disease in men. Circulation. 2000; 102(17): 2058-2062.
6.
Kohler HP, Futers TS, Grant PJFXII (46C0/T) polymorphism and in vivo generation of FXII activity. Thromb Haemost. 1999;81(5):745-747.
7.
Smith GD, Ebrahim S.Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol.2004;33(1):30-42.
8.
Kanaji T., Okamura T., Osaki K., et al. A common genetic polymorphism (46 C to T substitution) in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level. Blood. 1998;91(6):2010-2014.
9.
Kohler HP, Futers TS, Grant PJFXII (46C->T) polymorphism and in vivo generation of FXII activity-gene frequencies and relationship in patients with coronary artery disease. Thromb Haemost. 1999;81(5):745-747.
10.
Zito F., Drummond F., Bujac SR, et al. Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men. Circulation. 2000;102(17):2058-2062.
11.
Endler G., Exner M., Mannhalter C., et al. A common C->T polymorphism at nt 46 in the promoter region of coagulation factor XII is associated with decreased factor XII activity . Thromb Res. 2001;101(4):255-260.
12.
Soria JM, Almasy L., Souto JC, et al. A quantitative-trait locus in the human factor XII gene influences both plasma factor XII levels and susceptibility to thrombotic disease. Am J Hum Genet. 2002;70(3):567-574.
13.
Tirado I., Soria JM, Mateo J., et al. Association after linkage analysis indicates that homozygosity for the 46 C->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis. Thromb Haemost. 2004 ;91(5):899-904.
14.
Antonarakis SERecommendations for a nomenclature system for human gene mutations. Nomenclature Working Group. Hum Mutat . 1998;11(1):1-3.
15.
Bach J., Endler G., Winkelmann BR, et al. Coagulation factor XII (FXII) activity, activated FXII, distribution of FXII C46T gene polymorphism and coronary risk. J Thromb Haemost. 2008;6(2):291-296.
16.
Caamano J., Jaramillo PC, Lanas C., Lanas F., Salazar LA. Factor XII 46C -> T gene polymorphism in chilean subjects with coronary artery disease and controls. Med Princ Pract. . 2009;18(2):137-142.
17.
Zito F., Lowe GD, Rumley A., McMahon AD, Humphries SE the WOSCOPS Study GroupWest of Scotland Coronary Prevention Study and Association of the factor XII 46C>T polymorphism with risk of coronary heart disease (CHD) in the WOSCOPS study. Atherosclerosis. 2002;165(1):153-158.
18.
Roldán V., Corral J., Marín F., Pineda J., Vicente V., González-Conejero R.Synergistic association between hypercholesterolemia and the C46T factor XII polymorphism for developing premature myocardial infarction. Thromb Haemost. 2005;94(6): 1294-1299.
19.
Endler G., Mannhalter C., Sunder-Plassmann H., et al. Homozygosity for the C->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome. Br J Haematol. 2001;115(4):1007-1009.
20.
Santamaria A., Mateo J., Tirado I., et al. Homozygosity of the T allele of the 46 C->T polymorphism in the F12 gene is a risk factor for ischemic stroke in the Spanish population. Stroke. 2004;35(8):1795-1799.
21.
Reuner KH, Jenetzky E., Aleu A., et al. Factor XII C46T gene polymorphism and the risk of cerebral venous thrombosis. Neurology. 2008;70(2):129-132.
22.
Oguchi S., Ito D., Murata M., et al. Genotype distribution of the 46C->T polymorphism of coagulation factor XII in the Japanese population: absence of its association with ischemic cerebrovascular disease. Thromb Haemost. 2000 ;83(1):178-179.
23.
Renner W., Pabst E., Paulweber B., et al. The angiotensin-converting enzyme insertion/deletion polymorphism is not a risk factor for peripheral arterial disease. Atherosclerosis . 2002;165(1):175-178.
24.
Halperin JL, Creage MAArterial obstructive disease of the extremities. In: Loscalzo J, Creager MA, Dzau VJ, eds. Vascular Medicine. Boston: Little, Brown and Company;1996:825-852.
25.
Esterbauer H., Schneitler C., Oberkofler H., et al. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans . Nat Genet. 2001;28(2):178-183.
26.
Sanchez LA, Veith FJDiagnosis and treatment of chronic lower extremity ischemia. Vasc Med. 1998;3(4): 291-299.
27.
Alberti Kgmm , Zimmet PZDefinition, diagnosis and classification of diabetes mellitus and its complications part 1: diagnosis and classification of diabetes mellitus-provisional report of a WHO consultation. Diabet Med. 1998;15(7):539-553.
28.
Grunbacher G., Marx-Neuhold E., Pilger E., Koppel H., Renner W.The functional -4C>T polymorphism of the coagulation factor XII gene is not associated with deep venous thrombosis . J Thromb Haemost. 2005;3(12):2815-2817.
29.
Ishii K., Oguchi S., Murata M., et al. Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects. Blood Coagul Fibrinolys. 2000;11(3):277-284.
