Following new guidelines that contain recommendations on the desirable features of a genetic association study, we performed a case-control study to establish the risk of acute coronary artery disease (CAD) related to the polymorphism (46 C-->T) in the F12 gene. We found a 6-fold higher risk of acute CAD associated with the homozygosity of the T allele of the F12, 46C-->T polymorphism in the Spanish population.