Variant VKORC1 and CYP2C9 Alleles in Patients with Diffuse Alveolar Hemorrhage Caused by Oral Anticoagulants
Authors: Wijnen, Petal A.; Linssen, Catharina F.; Haenen, Guido R.; Bekers, Otto; Drent, Marjolein
Source: Molecular Diagnosis & Therapy, Volume 14, Number 1, 1 February 2010 , pp. 23-30(8)
Publisher: Adis International
Abstract:Background Diffuse alveolar hemorrhage (DAH) is a life-threatening bleeding complication that can occur as a result of oral anticoagulation therapy.
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.
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.
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.
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.
Document Type: Research Article
Affiliations: 3 Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands
Publication date: 2010-02-01