title: 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.
abstract: 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 A(1628) 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.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Second Medical University, China.
authors.forename: W
authors.initials: W
authors.lastname: Le
authors.forename: J D
authors.initials: JD
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: Tao
authors.forename: B
authors.initials: B
authors.lastname: You
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.forename: W J
authors.initials: WJ
authors.lastname: Cao
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: R M
authors.initials: RM
authors.lastname: He
authors.forename: D L
authors.initials: DL
authors.lastname: Zhu
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: L S
authors.initials: LS
authors.lastname: Gong
mesh_terms: D020016:Activated Protein C Resistance / Q000378:metabolism*; D000368:Aged; D002681:China / Q000453:epidemiology; D003327:Coronary Disease / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005091:Exons; D005165:Factor V / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D005165:Factor V