Inherited predisposition to thrombosis contributes to the initiation and progression of coronary artery disease (CAD). The present study was designed to explore the relationship between genetic variation of coagulation factor V and occurrence of CAD.
A total of 141 unrelated patients with CAD and 175 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) for variation detection in all 25 exons of the factor V gene. Among the study subjects, 55 CAD patients and 73 controls were evaluated at random for response to activated protein C (APC) by Coatest APC resistance test.
Polymorphisms in exon 4, 10, 13 and 16 of factor V gene were documented [642G→T(S156), 1628→A(R485K), 4070A→G(H1299R) and 5380G→A(V1736M), respectively]. The study also identified a novel polymorphism 327A→G in exon 2 which did not alter the amino acid residue. Leiden mutation (R506Q) was not detected in any of our 316 subjects. Among the five polymorphisms, the allele frequency of 1628G→A was significantly different between the CAD patients and the controls (0.36 vs. 0.21, p<0.05). Subjects homozygous or heterozygous for the A allele of 1628G→A polymorphism had lower normalized APC ratios than those with the GG genotype in the CAD group (1.16±0.13 and 1.18±0.23 vs. 1.36±0.33, p<0.05) and in the controls, indicating that A1628 allele was associated with a poor response to APC.
We conclude that the 1628G→A (R485K) polymorphism of factor V is associated with a poor response to APC and increased risk for CAD.