OBJECTIVE: Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial 3 to 6 months of acenocoumarol treatment. METHODS: A prospective follow-up study was performed at 2 anticoagulation clinics in the Netherlands. Included subjects started with a standard dose regimen as follows: 6 mg on the first day, 4 mg on the second day, and 2 mg on the third day. CYP2C9 genotypes were assessed, and data on international normalized ratio (INR), comedication, and comorbidity were collected. RESULTS: The CYP2C9 genotype of 231 subjects was assessed. Of these, 147 (63.6%) were wild-type subjects (CYP2C9*1/*1), 38 (16.5%) were carriers of CYP2C9*2, and 46 (19.9%) were carriers of CYP2C9*3. Compared with wild-type subjects, carriers of the CYP2C9*3 allele had (1) a lower chance to achieve stability in the first 6 months of therapy (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91; P <.05) and (2) an increased risk of severe overanticoagulation (INR >6.0) (hazard ratio, 3.80; 95% confidence interval, 1.54-9.39; P <.01). For both outcomes, there was no significant difference between carriers of the CYP2C9*2 allele and wild-type subjects. CONCLUSION: In carriers of the CYP2C9*3 allele more difficulties in terms of stabilization and overanticoagulation were found as compared with wild-type subjects or CYP2C9*2 carriers. CYP2C9 genotyping could be useful to identify potential candidates for more frequent INR controls to minimize problems with acenocoumarol anticoagulation status.
OBJECTIVE: Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial 3 to 6 months of acenocoumarol treatment. METHODS: A prospective follow-up study was performed at 2 anticoagulation clinics in the Netherlands. Included subjects started with a standard dose regimen as follows: 6 mg on the first day, 4 mg on the second day, and 2 mg on the third day. CYP2C9 genotypes were assessed, and data on international normalized ratio (INR), comedication, and comorbidity were collected. RESULTS: The CYP2C9 genotype of 231 subjects was assessed. Of these, 147 (63.6%) were wild-type subjects (CYP2C9*1/*1), 38 (16.5%) were carriers of CYP2C9*2, and 46 (19.9%) were carriers of CYP2C9*3. Compared with wild-type subjects, carriers of the CYP2C9*3 allele had (1) a lower chance to achieve stability in the first 6 months of therapy (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91; P <.05) and (2) an increased risk of severe overanticoagulation (INR >6.0) (hazard ratio, 3.80; 95% confidence interval, 1.54-9.39; P <.01). For both outcomes, there was no significant difference between carriers of the CYP2C9*2 allele and wild-type subjects. CONCLUSION: In carriers of the CYP2C9*3 allele more difficulties in terms of stabilization and overanticoagulation were found as compared with wild-type subjects or CYP2C9*2 carriers. CYP2C9 genotyping could be useful to identify potential candidates for more frequent INR controls to minimize problems with acenocoumarol anticoagulation status.
Authors: Nita A Limdi; Donna K Arnett; Joyce A Goldstein; T Mark Beasley; Gerald McGwin; Brian K Adler; Ronald T Acton Journal: Pharmacogenomics Date: 2008-05 Impact factor: 2.533
Authors: Bas J M Peters; Olaf H Klungel; Anthonius de Boer; Bruno H Ch Stricker; Anke-Hilse Maitland-van der Zee Journal: Clin Cases Miner Bone Metab Date: 2009-01
Authors: Talitha I Verhoef; William K Redekop; Ann K Daly; Rianne M F van Schie; Anthonius de Boer; Anke-Hilse Maitland-van der Zee Journal: Br J Clin Pharmacol Date: 2014-04 Impact factor: 4.335
Authors: N A Limdi; G McGwin; J A Goldstein; T M Beasley; D K Arnett; B K Adler; M F Baird; R T Acton Journal: Clin Pharmacol Ther Date: 2007-07-25 Impact factor: 6.875