Association of the R485K polymorphism of the factor V gene with poor response to activated protein C and increased risk of coronary artery disease inthe Chinese population

Inherited predisposition to thrombosis contributes to the initiation and pr ogression 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 an alyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) for variation detection in all 25 exons of the factor V gene. A mong 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 [64 2G --> A(S156), 1628 --> A(R485K), 4070A --> G(H1299R) and 5380G --> A(V173 6M), respectively]. The study also identified a novel polymorphism 327A --> G in exon 2 which did not alter the amino acid residue. Leiden mutation (R 506Q) was not detected in ally of our 316 subjects. Among the five polymorp hisms, the allele frequency of 1628G --> A was significantly different betw een the CAD patients and the controls (0.36 vs. 0.21, p < 0.05). Subjects h omozygous or heterozygous for the A allele of 1628G --> A polymorphism had lower normalized APC ratios than those with the GG genotype in the CAD grou p (1.16 +/- 0.13 and 1.18 +/- 0.23 vs, 1.36 +/- 0.33, p < 0.05) and in the controls, indicating that A(1628) allele was associated with a poor respons e to APC. We conclude that the 1628G --> A (R485K) polymorphism of factor V is associ ated with a poor response to APC and increased risk for CAD.