Coagulation factor XII (FXII) activity, activated FXII, distribution of FXII C46T gene polymorphism and coronary risk.
Whether factor XII (FXII) activity, its 46C>T polymorphism and activated FXII (FXIIa) are associated with coronary heart disease (CHD) remains to be determined.



FXII, FXIIa and the FXII 46C>T polymorphism were determined in a hospital-based cohort of 2615 patients undergoing coronary angiography.



Fifty-seven per cent of the participants were identified as wild-type (46CC), 38% as heterozygous (46CT) and 5% as homozygous (46TT) for FXII 46C>T. FXII and FXIIa levels were significantly lower in carriers of the T-allele: 132 (97-151) U dL(-1) FXII in 46CC, 87 (77-99) U dL(-1) FXII in 46CT and 53 (42-67) U dL(-1) FXII in 46TT carriers (P < 0.001), and 2.8 (2.3-3.5) microg L(-1) FXIIa in CC, 2.1 (1.6-2.6) microg L(-1) FXIIa in CT and 1.2 (0.9-1.5) microg L(-1) FXIIa in TT carriers (P < 0.001; medians, lower and upper quartiles). Patients with stable CHD (n = 935), a history of myocardial infarction (n = 785) or who were suffering from acute coronary syndromes (ACS; n = 323) had significantly lower FXII levels than controls (n = 572). The differences remained statistically significant after adjustments for age, sex, diabetes mellitus, smoking, hypercholesterolemia and hypertension. Significantly reduced FXIIa levels in ACS patients lost significance once adjusted for covariates. FXII genotype was not associated with any clinical phenotype.



Lower FXII activity represents an independent risk for CHD and ACS. This is not the case for FXIIa levels or the FXII 46C>T variation.
Bach
J
J
Institute of Hemostaseology and Transfusion Medicine, Academic City Hospital, Ludwigshafen, Germany.
Endler
G
G
Winkelmann
B R
BR
Boehm
B O
BO
Maerz
W
W
Mannhalter
C
C
Hellstern
P
P
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015897:Comorbidity; D003327:Coronary Disease / Q000453:epidemiology*; D005174:Factor XII / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005175:Factor XII Deficiency / Q000453:epidemiology*; D015956:Factor XIIa / Q000032:analysis / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D044465:White People / Q000235:genetics
D005174:Factor XII; D015956:Factor XIIa