The objective of this study was to determine the additional contribution ofNQO1andCYP4F2genotypes to warfarin dose requirements across two racial groups after accounting for known clinical and genetic predictors.Patients & methods:
The following were assessed in a cohort of 260 African–Americans and 53 Hispanic–Americans: clinical data;NQO1p.P187S (*1/*2);CYP2C9*2, *3, *5, *6, *8and*11;CYP4F2p.V433M; andVKORC1c.-1639G>A genotypes.Results:
Both theCYP4F2433M (0.23 vs 0.06; p < 0.05) andNQO1*2(0.27 vs 0.18; p < 0.05) allele frequencies were higher in Hispanic–Americans compared with African–Americans. Multiple regression analysis in the Hispanic–American cohort revealed that eachCYP4F2433M allele was associated with a 22% increase in warfarin maintenance dose (p = 0.019). Possession of theNQO1*2allele was associated with a 34% increase in warfarin maintenance dose (p = 0.004), while adjusting for associated genetic (CYP2C9,CYP4F2andVKORC1) and clinical factors. In this population, the inclusion ofCYP4F2andNQO1*2genotypes improved the dose variability explained by the model from 0.58 to 0.68 (p = 0.001), a 17% relative improvement. By contrast, there was no association betweenCYP4F2orNQO1*2genotype and therapeutic warfarin dose in African–Americans after adjusting for known genetic and clinical predictors.Conclusion:
In our cohort of inner-city Hispanic–Americans, theCYP4F2andNQO1*2genotypes significantly contributed to warfarin dose requirements. If our findings are confirmed, they would suggest that inclusion of theCYP4F2andNQO1*2genotypes in warfarin dose prediction algorithms may improve the predictive ability of such algorithms in Hispanic–Americans.