Synergistic association between hypercholesterolemia and the C46T factor XII polymorphism for developing premature myocardial infarction

Factor XII (FXII) plays a key role in both coagulation and fibrinolysis, thus its role in thrombotic processes is uncertain. Both genetic and environmental factors determine FXII plasma levels. A common C46T polymorphism in the Kozak region of F12 gene disturbs the translation of the protein leading to a significant reduction of FXII levels although its clinical significance is conflictive.We studied the F12 C46T polymorphism in 281 patients who had suffered from an acute myocardial infarction (MI) before 45-year-old and 550 control subjects from the same area. Serum levels of cholesterol, HDL, LDL, triglycerides and C reactive protein (CRP) were assayed in the MI group.The 46T allele slightly increased the risk to suffer from premature MI (OR: 1.64; 95%Cl: 1.14-2.37; p= 0.008). Moreover, patients carrying the 46T allele showed increased levels of CRP (p= 0.002). Interestingly, we found that the simultaneous presence of the 46T allele and hypercholesterolemia increases the risk to develop premature MI 2.26 times. The F12 C46T polymorphism, associated with a reduction of plasma FXII levels, seems to play a deleterious effect, predisposing the development of premature MI, especially in hypercholesterolemic patients.This effect could be associated with an increased pro-inflammatory state, as the 46T allele associates with high levels of CRP.