Table 4.
Multivariable evaluation of the association of individual VKORC1 SNPs with log warfarin maintenance dose among POAT participants by race.
| SNP-ID* | Standard coordinates |
Additive model‡ |
Dominant model§ |
||||
|---|---|---|---|---|---|---|---|
| r2model (%) | r2vkor (%) | r22C9 (%) | r2model (%) | r2vkor (%) | r22C9 (%) | ||
| European–Americans | |||||||
| rs7294 | 3730G/A | 34.0 | 5.2 | 12.2 | 30.3 | 5.3 | 8.8 |
| rs2359612 | 2255C/T | 46.5 | 18.1 | 12.4 | 37.2 | 12.8 | 8.3 |
| rs8050894 | 1542G/C | 47.5 | 19.1 | 12.2 | 38.0 | 13.6 | 8.1 |
| rs9934438 | 1173C/T | 46.8 | 18.4 | 12.3 | 37.3 | 12.8 | 8.6 |
| rs17708472 | 698C/T | 33.1 | 5.2 | 11.3 | 28.8 | 4.4 | 7.0 |
| rs2884737 | 497T/G | 36.3 | 7.9 | 12.5 | 31.0 | 6.6 | 8.6 |
| rs9923231 | −1639G/A | 46.0 | 17.2 | 12.3 | 36.3 | 12.2 | 8.0 |
| rs7196161 | −4931T/C | 45.7 | 16.8 | 11.6 | 35.1 | 10.6 | 8.1 |
| African–Americans | |||||||
| rs17882368 | 5729T/C | 38.1 | 4.3 | 3.2 | 36.5 | 4.2 | 1.6 |
| rs7294 | 3730G/A | 35.0 | 1.3 | 2.2 | 33.4 | 1.1 | 1.0 |
| rs2359612 | 2255C/T | 39.0 | 5.4 | 2.4 | 37.3 | 5.0 | 0.9 |
| rs9934438 | 1173C/T | 38.6 | 4.9 | 3.2 | 36.9 | 4.7 | 1.5 |
| rs9923231 | −1639G/A | 38.9 | 4.3 | 3.2 | 37.2 | 3.9 | 1.5 |
SNPs explaining <1.0% variability in warfarin dose were not evaluated in multivariable analyses.
Standard coordinate is relative to the ATG start codon defined as +1 in Genbank Accession No. AY587020.
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 VKORC1 SNP 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 SNP for African–Americans.
VKORC1 and CYP2C9 genotypes were included as covariates with three levels in the additive models.
VKORC1 and CYP2C9 genotypes were included as covariates with two levels (wild-type vs variant) in the dominant models.
Statistically nonsignificant at α = 0.05. All other associations were significant at α <0.05.
r2model: Percent variation in warfarin dose explained by the model containing clinical and genetic covariates; r2vkor: Semi-partial r2 denoting percent variation in warfarin dose explained by VKORC1 SNP; r22C9 :Semi-partial r2 denoting percent variation in warfarin dose explained by CYP2C9 (variant includes *2, *3, *5, *6 and *11 alleles for African–Americans; *2 and *3 for European–Americans) genotype.
CHF: Congestive heart failure; HMG: 3-hydroxy-3-methylglutaryl; POAT: Pharmacogenetic Optimization of Anticoagulation Therapy.