Activated factor XII levels and factor XII 46C >T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects

The relationship of activated factor XII (FXIIa) and FXII 46C > T genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type I diabetic subjects (mean age 38 +/- 4 years). Coronary artery calcification (CAC) was measured using Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function, and FXIIa were measured by ELISA. Endothelial nitric oxide production was quantified as the forearm blood flow response to intra-brachial infusion of bradykinin and N-G monomethyl-L-arginine (L-NMMA). A higher FXIIa was independently associated with higher triglycerides (P < 0.001), BMI (P = 0.001), alcohol consumption (P = 0.003) and vWF (P < 0.001) in non-diabetic subjects and with insulin dose (P = 0.009), total cholesterol (P = 0.02) and alcohol (P < 0.001) in diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non-diabetic subjects (1.92 ng/ml, P < 0.001). Higher FXIIa was associated with lower response to bradykinin (P = 0.048) and to L-NMMA (P = 0.029). FXIIa was positively associated with CAC (odds ratio = 1.57 for every I ng/ml higher FXIIa, P = 0.005) but not independently of other risk factors (odds ratio = 1.1 on adjustment). 46C > T genotype explained 18% of the variance in FXIIa (P < 0.001) but was not associated with CAC (P = 0.6). We conclude that plasma FXIIa is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction. FXIIa appears unlikely to be directly atherogenic but may be a useful marker of coronary atherosclerosis because of its association with these other factors. Type I diabetes is associated with lower levels of FXIIa despite a greater prevalence of atherosclerosis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.