Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAFI) with blood pressure

Thrombin-activable fibrinolysis inhibitor (TAFI) is a hepatically secreted zymogen, whose substrates include bradykinin. The CPB2 gene encoding TAF1 i s a candidate gene for blood pressure. A recently identified single nucleot ide polymorphism (SNP) in the CPB2 coding region., designated as 1057C > T, results in an amino acid change at TAFI residue 325 (Ile > Thr325). We fou nd that the genotype based on this SNP was significantly associated with bl ood pressure in aboriginal Canadians. Specifically, analysis of variance sh owed that homozygotes for CPB2 1057T had significantly lower diastolic bloo d pressure than subjects with other CPB2 genotypes. CPB2 genotype accounted for similar to3% of the total variation in diastolic blood pressure, consi stent with the expected magnitude of a modest genetic effect in a complex t rait such as blood pressure. Although the mechanism underlying the associat ion is unclear, the findings are of interest because TAF1 may provide a lin k between coagulation and blood pressure regulation.