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Variant VKORC1 and CYP2C9 alleles in patients with diffuse alveolar hemorrhage caused by oral anticoagulants.
- Source :
-
Molecular diagnosis & therapy [Mol Diagn Ther] 2010 Feb 01; Vol. 14 (1), pp. 23-30. - Publication Year :
- 2010
-
Abstract
- Background: Diffuse alveolar hemorrhage (DAH) is a life-threatening bleeding complication that can occur as a result of oral anticoagulation therapy.<br />Objective: We hypothesized that in patients treated with coumarins, alveolar hemorrhage is associated with vitamin K epoxide reductase (VKORC1) and cytochrome P450 (CYP) 2C9 (CYP2C9) variant alleles. In addition, in the case of acenocoumarol use, CYP2C19 allelic variants also play a role.<br />Methods: During a 7-year period, data on patients using coumarins with confirmed DAH were gathered. Of 173 confirmed DAH cases, 75 received oral anticoagulants, and 63 (84%) of these 75 patients were included because their DNA was available. For genotyping the CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), CYP2C19*2 (681G>A), CYP2C19*3 (636G>A), VKORC1 (-1639G>A), and VKORC1 (1173C>T) single nucleotide polymorphisms (SNPs), real-time PCRs were performed.<br />Results: In 62 (98.4%) of 63 patients with DAH, variant alleles were found. In 51 (81.0%) of the 63 patients, VKORC1 allelic variants (20 homozygotes and 31 heterozygotes) were present. In 31 (49.2%) of the 63 DAH cases, CYP2C9 allelic variants (three homozygotes, 26 heterozygotes, and two compound heterozygotes) were observed, and in 20 (32.0%) of the 63 patients, variant alleles of both genes were observed.<br />Conclusion: Genotyping of four SNPs for VKORC1 and CYP2C9 polymorphisms is useful in predicting a high probability of the occurrence of DAH in patients receiving oral anticoagulants. Early and timely use of genotyping is recommended to prevent a fatal outcome and to provide safer and more individualized anticoagulant therapy.
- Subjects :
- Administration, Oral
Anticoagulants administration & dosage
Coumarins administration & dosage
Coumarins adverse effects
Cytochrome P-450 CYP2C9
Genetic Predisposition to Disease genetics
Genotype
Hemorrhage chemically induced
Humans
Lung Diseases chemically induced
Polymerase Chain Reaction
Polymorphism, Single Nucleotide genetics
Pulmonary Alveoli drug effects
Pulmonary Alveoli pathology
Vitamin K Epoxide Reductases
Anticoagulants adverse effects
Aryl Hydrocarbon Hydroxylases genetics
Hemorrhage genetics
Lung Diseases genetics
Mixed Function Oxygenases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1179-2000
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular diagnosis & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 20121287
- Full Text :
- https://doi.org/10.2165/11530890-000000000-00000