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


Corresponding author: JDYu, MD, PhD, Department of Cardiology, Rui Jin Hospital, Shanghai Second Medical University, 197 Rui Jin 2nd Road, Shanghai 200025, China. Fax: +86 21 64333548


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.