[Cytochrome P450 2C9 polymorphisms (CYP2C9) and warfarin maintenance dose in elderly patients].
OBJECTIVE
Allelic variants of the gene coding for cytochrome P450 isoform 2C9 (CYP2C9), 2C9*2 and 2C9*3, were shown to increase sensitivity to warfarin in adults. In the elderly, the maintenance dose is influenced by acquired factors including comorbidities and polymedication. The aim of our purpose was to investigate whether a genetic factor, such as cyp2c9 genotype, does influence the warfarin maintenance dose in very elderly patients.


METHODS
In-patients treated with warfarin were recruited with the following inclusion criteria: i/ 75 years-old or over; ii/ a stable INR within the therapeutic range (INR 2.0-3.0). Genotypes were coded as numbers of alleles for each of the three polymorphisms, namely 2C9*1 (wild-type), 2C9*2, and 2C9*3.


RESULTS
CYP2C9 genotype was performed in 126 patients, mean age 87 +/-6 years (75-103), 29 males-97 females. The mean daily dose of warfarin was 3.0 +/-1.4 mg, with 3.1 mg in patients with the wild-type *1/*1 genotype (n =80), 2.7 mg in *1/*2 heterozygotes (n =20), 2.9 mg in *1/*3 heterozygotes (n =18), 1.2 mg in *2/*2 homozygotes (n =2), 2.3 mg in compound heterozygotes *2/*3 (n =6). The relationships between dose and potential factors were assessed using the correlation coefficient test for age and Fischer exact tests for the categorical variables. The only factors significantly linked to the dose were the numbers of 2C9*1 and 2C9*2 alleles.


CONCLUSIONS
In elderly patients, a genetic influence on response to warfarin does exist as in younger patients.
Siguret
V
V
Laboratoire d'hématologie, hôpital Charles-Foix, 7, avenue de la République, 94205 Ivry-sur-Seine cedex, France. virginie.siguret@cfx.ap-hop-paris.fr
Gouin
I
I
Golmard
J-L
JL
Geoffroy
S
S
Andreux
J-P
JP
Pautas
E
E
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000494:pharmacology*; D015897:Comorbidity; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology
D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases