Table 7.
Influence of genetic and nongenetic covariates on warfarin dose among European–Americans and African–Americans.
| Fold change |
||||
|---|---|---|---|---|
| Characteristic | Additive model |
Dominant model |
||
| European–American | African–American | European–American | African–American | |
| Age* | 0.99 | 0.99 | 0.99 | 0.99 |
| Female | 0.87 | 0.81 | 0.88 | 0.81 |
| BMI‡ | 1.01 | 1.01 | 1.01 | 1.01 |
| Current drinker | – | 1.01 | – | 1.01 |
| Intake of vitamin K-rich foods§ | 1.04 | 1.03 | 1.05 | 1.03 |
| Congestive heart failure | 0.93 | 0.94 | 0.92 | 0.94 |
| Renal failure | – | 0.85 | – | 0.84 |
| HMG coenzyme A inhibitor | 1.10 | 0.94 | 1.10 | 0.94 |
| Amiodarone | 0.81 | 0.78 | 0.82 | 0.79 |
| CYP2C9 genotype¶ | 0.75 | 0.83 | 0.75 | 0.84 |
| VKORC1 1173C/T genotype | 0.74 | 0.80 | 0.71 | 0.79 |
| Average dose (mg/day) | 6.3 | 6.7 | 6.0 | 6.7 |
Log transformation of dose was performed for analyses. Above we present the re-transformed (back-transformed) dose. The fold changes are to be applied to the back-transformed dose. Multivariable model adjusted for significant (p < 0.2) clinical covariates (age, gender BMI, average vitamin K intake, presence of CHF, use of HMG-coenzyme A inhibitors, use of amiodarone) and CYP2C9 and the single VKORC 1173C/T for European–Americans. Multivariable model adjusted for significant (p < 0.2) clinical covariates (age, gender BMI, smoking, average vitamin K intake, average alcohol intake, presence of renal failure, presence of CHF, use of HMG-coenzyme A inhibitors, use of amiodarone) and CYP2C9 and the single VKORC1 1173C/T for African–Americans
VKORC1 and CYP2C9 genotypes were included as covariates with three levels in the additive models. Fold change is per copy of variant allele.
VKORC1 and CYP2C9 genotypes were included as covariates with two levels (wild-type versus variant) in the dominant models.
Per year increase over 61 years.
Per unit increase over BMI of 30.
Per serving of vitamin K-rich foods.
CYP2C9 variant genotype includes *2, *3 alleles among European–Americans and *2, *3, *5, *6 and *11 alleles among African–Americans. The referent patient is a 61-year-old man with BMI of 30, who is wild-type for CYP2C9 and VKORC1, a current nonsmoker and nondrinker, with no comorbidities (e.g., CHF, cancer) and no inhibitors of CYP2C9 (e.g., amiodarone), HMG coenzyme A inhibitors (patients were not on fluvastatin).
CHF: Congestive heart failure; HMG: 3-hydroxy-3-methylglutaryl.