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 | W Le, J D Yu, L Lu, R Tao, B You, X Cai, W J Cao, W Huang, R M He, D L Zhu, Z Chen, L S Gong |
Journal | Clinical genetics
(Clin Genet)
Vol. 57
Issue 4
Pg. 296-303
(Apr 2000)
ISSN: 0009-9163 [Print] Denmark |
PMID | 10845571
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Activated Protein C Resistance
(metabolism)
- Aged
- China
(epidemiology)
- Coronary Disease
(blood, ethnology, genetics)
- Electrophoresis, Agar Gel
- Exons
- Factor V
(genetics)
- Female
- Gene Frequency
- Genotype
- Humans
- Male
- Middle Aged
- Partial Thromboplastin Time
- Point Mutation
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Risk Factors
- Sequence Analysis, DNA
|