The Future of Warfarin Pharmacogenetics in under-represented Minority Groups

• Hylek EM , Evans-MolinaC, SheaC, HenaultLE, ReganS. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with a trial fibrillation. Circulation, 115(21), 2689–2696 (2007).
   PubMed Web of Science ®Google Scholar
• Hylek EM , GoAS, ChangYet al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N. Engl. J. Med. , 349(11), 1019–1026 (2003).
   PubMed Web of Science ®Google Scholar
• Wadelius M , ChenLY, LindhJDet al. The largest prospective warfarin-treated cohort supports genetic forecasting. Blood , 113(4), 784–792 (2009).
   PubMed Web of Science ®Google Scholar
• Budnitz DS , LovegroveMC, ShehabN, RichardsCL. Emergency hospitalizations for adverse drug events in older Americans. N. Engl. J. Med., 365(21), 2002–2012 (2011).
   PubMed Web of Science ®Google Scholar
• Ansell J , HirshJ, HylekEet al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest , 133(Suppl. 6), S160–S198 (2008).
   PubMed Web of Science ®Google Scholar
• Hirsh J , FusterV, AnsellJ, HalperinJL. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation, 107(12), 1692–1711 (2003).
   PubMed Web of Science ®Google Scholar
• Klein TE , AltmanRB, ErikssonNet al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N. Engl. J. Med. , 360(8), 753–764 (2009).
   PubMed Web of Science ®Google Scholar
• Absher RK , MooreME, ParkerMH. Patient-specific factors predictive of warfarin dosage requirements. Ann. Pharmacother., 36(10), 1512–1517 (2002).
   PubMed Web of Science ®Google Scholar
• Limdi NA , LimdiMA, CavallariLet al. Warfarin dosing in patients with impaired kidney function. Am. J. Kidney Dis. , 56(5), 823–831 (2010).
   PubMed Web of Science ®Google Scholar
• Huang SW , ChenHS, WangXQet al. Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose: a prospective study in Chinese patients. Pharmacogenet. Genomics , 19(3), 226–234 (2009).
   PubMed Web of Science ®Google Scholar
• Gage BF , EbyC, JohnsonJAet al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin. Pharmacol. Ther. , 84(3), 326–331 (2008).
   PubMed Web of Science ®Google Scholar
• Anderson JL , HorneBD, StevensSMet al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation , 116(22), 2563–2570 (2007).
   PubMed Web of Science ®Google Scholar
• Burmester JK , BergRL, YaleSHet al. A randomized controlled trial of genotype-based coumadin initiation. Genet. Med. , 13(6), 509–518 (2011).
   PubMed Web of Science ®Google Scholar
• Rieder MJ , ReinerAP, GageBFet al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N. Engl. J. Med. , 352(22), 2285–2293 (2005).
   PubMed Web of Science ®Google Scholar
• Cooper GM , JohnsonJA, LangaeeTYet al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. Blood , 112(4), 1022–1027 (2008).
   PubMed Web of Science ®Google Scholar
• Cha PC , MushirodaT, TakahashiAet al. Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese. Hum. Mol. Genet. , 19(23), 4735–4744 (2011).
   Web of Science ®Google Scholar
• Takeuchi F , McGinnisR, BourgeoisSet al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet. , 5(3), E1000433 (2009).
   PubMed Web of Science ®Google Scholar
• Limdi NA , ArnettDK, GoldsteinJAet al. Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European–Americans and African–Americans. Pharmacogenomics , 9(5), 511–526 (2008).
   PubMed Web of Science ®Google Scholar
• Scordo MG , PengoV, SpinaEet al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin. Pharmacol. Ther. , 72(6), 702–710 (2002).
   PubMed Web of Science ®Google Scholar
• Takahashi H , KashimaT, NomizoYet al. Metabolism of warfarin enantiomers in Japanese patients with heart disease having different CYP2C9 and CYP2C19 genotypes. Clin. Pharmacol. Ther. , 63(5), 519–528 (1998).
   PubMed Web of Science ®Google Scholar
• Cavallari LH , LangaeeTY, MomaryKMet al. Genetic and clinical predictors of warfarin dose requirements in African Americans. Clin. Pharmacol. Ther. , 87(4), 459–464 (2010).
   PubMed Web of Science ®Google Scholar
• Limdi NA , McGwinG, GoldsteinJAet al. Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African–American and European–American patients on warfarin. Clin. Pharmacol. Ther. , 83(2), 312–321 (2007).
   PubMed Web of Science ®Google Scholar
• Rost S , FreginA, IvaskeviciusVet al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature , 427(6974), 537–541 (2004).
   PubMed Web of Science ®Google Scholar
• D‘Andrea G , D‘AmbrosioRLet al., Di Perna P A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood, 105(2), 645–649 (2005).
   PubMed Web of Science ®Google Scholar
• Wang D , ChenH, MomaryKMet al. Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement. Blood , 112(4), 1013–1021 (2008).
   PubMed Web of Science ®Google Scholar
• Limdi NA , WadeliusM, CavallariLet al. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood , 115(18), 3827–3834 (2010).
   PubMed Web of Science ®Google Scholar
• Coumadin ®, package insert. Bristol-Myers Squibb, Princeton, NJ, USA.
   Google Scholar
• Gage BF , EbyC, MilliganPEet al. Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb. Haemost. , 91(1), 87–94 (2004).
   PubMed Web of Science ®Google Scholar
• Lenzini P , WadeliusM, KimmelSet al. Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin. Pharmacol. Ther. , 87(5), 572–578 (2010).
   PubMed Web of Science ®Google Scholar
• Horne BD , LenziniPA, WadeliusMet al. Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy. Thromb. Haemost. , 107(2), 232–240 (2012).
   PubMed Web of Science ®Google Scholar
• Aithal GP , DayCP, KestevenPJ, DalyAK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet, 353(9154), 717–719 (1999).
   PubMed Web of Science ®Google Scholar
• Lindh JD , HolmL, AnderssonML, RaneA. Influence of CYP2C9 genotype on warfarin dose requirements – a systematic review and meta-analysis. Eur. J. Clin. Pharmacol., 65(4), 365–375 (2009).
   PubMed Web of Science ®Google Scholar
• Cavallari LH , MomaryKM, PatelSRet al. Pharmacogenomics of warfarin dose requirements in Hispanics. Blood Cells Mol. Dis. , 46(2), 147–150 (2011).
   PubMed Web of Science ®Google Scholar
• Perera MA , GamazonE, CavallariLHet al. The missing association: sequencing-based discovery of novel SNPs in VKORC1 and CYP2C9 that affect warfarin dose in African Americans. Clin. Pharmacol. Ther. , 89(3), 408–415 (2011).
   PubMed Web of Science ®Google Scholar
• Limdi NA , BeasleyTM, CrowleyMRet al. VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African–Americans and European–Americans. Pharmacogenomics, 9(10), 1445–1458 (2008).
   PubMed Web of Science ®Google Scholar
• Marsh S , KingCR, Porche-SorbetRM, Scott-HortonTJ, EbyCS. Population variation in VKORC1 haplotype structure. J. Thromb. Haemost., 4(2), 473–474 (2006).
   PubMed Web of Science ®Google Scholar
• Voora D , KoboldtDC, KingCRet al. A polymorphism in the VKORC1 regulator calumenin predicts higher warfarin dose requirements in African Americans. Clin. Pharmacol. Ther. , 87(4), 445–451 (2010).
   PubMed Web of Science ®Google Scholar
• Cavallari LH , PereraM, WadeliusMet al. Association of the GGCX (CAA)16/17 repeat polymorphism with higher warfarin dose requirements in African Americans. Pharmacogenet. Genomics , 22(2), 152–158 (2012).
   PubMed Web of Science ®Google Scholar
• Caldwell MD , AwadT, JohnsonJAet al. CYP4F2 genetic variant alters required warfarin dose. Blood, 111(8), 4106–4112 (2008).
   PubMed Web of Science ®Google Scholar
• Schneider D , LilienfeldDE, ImW. The epidemiology of pulmonary embolism: racial contrasts in incidence and in-hospital case fatality. J. Natl Med. Assoc., 98(12), 1967–1972 (2006).
   PubMed Web of Science ®Google Scholar
• Roger VL , GoAS, Lloyd-JonesDMet al. Heart disease and stroke statistics – 2011 update: a report from the American Heart Association. Circulation , 123(4), E18–E209 (2011).
   PubMed Web of Science ®Google Scholar
• White RH , DagerWE, ZhouH, MurinS. Racial and gender differences in the incidence of recurrent venous thromboembolism. Thromb. Haemost., 96(3), 267–273 (2006).
   PubMed Web of Science ®Google Scholar
• Morgenstern LB , SmithMA, LisabethLDet al. Excess stroke in Mexican Americans compared with non-Hispanic Whites: the brain attack surveillance in corpus christi project. Am. J. Epidemiol. , 160(4), 376–383 (2004).
   PubMed Web of Science ®Google Scholar
• Lisabeth LD , SmithMA, SanchezBN, BrownDL. Ethnic disparities in stroke and hypertension among women: the BASIC project. Am. J. Hypertens., 21(7), 778–783 (2008).
   PubMed Web of Science ®Google Scholar
• Lisabeth LD , RisserJM, BrownDLet al. Stroke burden in Mexican Americans: the impact of mortality following stroke. Ann. Epidemiol. , 16(1), 33–40 (2006).
   PubMed Web of Science ®Google Scholar
• White RH , KeenanCR. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb. Res., 123(Suppl. 4), S11–S17 (2009).
   PubMed Web of Science ®Google Scholar
• Price AL , WealeME, PattersonNet al. Long-range LD can confound genome scans in admixed populations. Am. J. Hum. Genet. , 83(1), 132–135; author reply 135–139 (2008).
   PubMed Web of Science ®Google Scholar
• Caldwell MD , BergRL, ZhangKQet al. Evaluation of genetic factors for warfarin dose prediction. Clin. Med. Res. , 5(1), 8–16 (2007).
   PubMedGoogle Scholar
• Momary KM , ShapiroNL, VianaMAet al. Factors influencing warfarin dose requirements in African–Americans. Pharmacogenomics , 8(11), 1535–1544 (2007).
   PubMed Web of Science ®Google Scholar
• Millican E , Jacobsen-LenziniPA, MilliganPEet al. Genetic-based dosing in orthopaedic patients beginning warfarin therapy. Blood , 110(5), 1511–1515 (2007).
   PubMed Web of Science ®Google Scholar
• Schelleman H , ChenJ, ChenZet al. Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans. Clin. Pharmacol. Ther. , 84(3), 332–339 (2008).
   PubMed Web of Science ®Google Scholar
• Gan GG , PhippsME, LeeMMet al. Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations. Ann. Hematol. , 90(6), 635–641 (2011).
   PubMed Web of Science ®Google Scholar
• Zhao F , LokeC, RankinSCet al. Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose. Clin. Pharmacol. Ther. , 76(3), 210–219 (2004).
   PubMed Web of Science ®Google Scholar
• Yu HC , ChanTY, CritchleyJA, WooKS. Factors determining the maintenance dose of warfarin in Chinese patients. QJM, 89(2), 127–135 (1996).
   PubMedGoogle Scholar
• Tishkoff SA , DietzschE, SpeedWet al. Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science , 271(5254), 1380–1387 (1996).
   PubMed Web of Science ®Google Scholar
• Dickmann LJ , RettieAE, KnellerMBet al. Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans. Mol. Pharmacol. , 60(2), 382–387 (2001).
   PubMed Web of Science ®Google Scholar
• Allabi AC , GalaJL, HorsmansY. CYP2C9 CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a Black Beninese population. Pharmacogenet. Genomics, 15(11), 779–786 (2005).
   PubMed Web of Science ®Google Scholar
• Blaisdell J , Jorge-NebertLF, CoulterSet al. Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics , 14(8), 527–537 (2004).
   PubMedGoogle Scholar
• Allabi AC , GalaJL, HorsmansYet al. Functional impact of CYP2C95, CYP2C96, CYP2C98, and CYP2C911in vivo among black Africans. Clin. Pharmacol. Ther. , 76(2), 113–118 (2004).
   PubMed Web of Science ®Google Scholar
• Lui Y , Hyun-YoungJ, TakahashiHet al. Decreased warfarin clearance with the CYP2C9 R150H (*8) polymorphism. Clin. Pharmacol. Ther. , 91(4), 660–665 (2012).
   PubMed Web of Science ®Google Scholar
• Mitchell C , GregersenN, KrauseA. Novel CYP2C9 and VKORC1 gene variants associated with warfarin dosage variability in the South African black population. Pharmacogenomics, 12(7), 953–963 (2011).
   PubMed Web of Science ®Google Scholar
• McDonald MG , RiederMJ, NakanoM, HsiaCH, RettieAE. CYP4F2 is a vitamin K1 oxidase: an explanation for altered warfarin cose in carriers of the V433M variant. Mol. Pharmacol., 75(6), 1337–1346 (2009).
   PubMed Web of Science ®Google Scholar
• Wajih N , SaneDC, HutsonSM, WallinR. The inhibitory effect of calumenin on the vitamin K-dependent γ-carboxylation system. Characterization of the system in normal and warfarin-resistant rats. J. Biol. Chem., 279(24), 25276–25283 (2004).
   PubMed Web of Science ®Google Scholar
• Shahin MH , KhalifaSI, GongYet al. Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. Pharmacogenet. Genomics , 21(3), 130–135 (2011).
   PubMed Web of Science ®Google Scholar
• Rost S , FreginA, KochDet al. Compound heterozygous mutations in the γ-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. Br. J. Haematol. , 126(4), 546–549 (2004).
   PubMed Web of Science ®Google Scholar
• Kimura R , MiyashitaK, KokuboYet al. Genotypes of vitamin K epoxide reductase, γ-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. Thromb. Res. , 120(2), 181–186 (2007).
   PubMed Web of Science ®Google Scholar
• Chen LY , ErikssonN, GwilliamRet al. Gamma-glutamyl carboxylase (GGCX) microsatellite and warfarin dosing. Blood , 106(10), 3673–3674 (2005).
   PubMed Web of Science ®Google Scholar
• King CR , DeychE, MilliganPet al. γ-glutamyl carboxylase and its influence on warfarin dose. Thromb. Haemost. , 104(4), 750–754 (2010).
   PubMed Web of Science ®Google Scholar
• Schwarz UI , RitchieMD, BradfordYet al. Genetic determinants of response to warfarin during initial anticoagulation. N. Engl. J. Med. , 358(10), 999–1008 (2008).
   PubMed Web of Science ®Google Scholar
• Wu AH , WangP, SmithAet al. Dosing algorithm for warfarin using CYP2C9 and VKORC1 genotyping from a multi-ethnic population: comparison with other equations. Pharmacogenomics , 9(2), 169–178 (2008).
   PubMed Web of Science ®Google Scholar
• Lubitz SA , ScottSA, RothlaufEBet al. Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population. J. Thromb. Haemost. , 8(5), 1018–1026 (2010).
   PubMed Web of Science ®Google Scholar
• Huang RS , JohnattySE, GamazonERet al. Platinum sensitivity-related germline polymorphism discovered via a cell-based approach and analysis of its association with outcome in ovarian cancer patients. Clin. Cancer. Res. , 17(16), 5490–5500 (2011).
   PubMed Web of Science ®Google Scholar
• Gamazon ER , ZhangW, KonkashbaevAet al. SCAN: SNP and copy number annotation. Bioinformatics , 26(2), 259–262 (2010).
   PubMed Web of Science ®Google Scholar
• Innocenti F , CooperGM, StanawayIBet al. Identification, replication, and functional fine-mapping of expression quantitative trait loci in primary human liver tissue. PLoS Genet. , 7(5), E1002078 (2011).
   PubMed Web of Science ®Google Scholar
• Perera MA , LimdiNA, CavallariLet al. Novel SNPs associated with warfarin dose in a large multicenter cohort of African Americans: Genome wide association study and replication results. Circulation , 124(Suppl. 1), 15518 (2011).
   Google Scholar
• Gamazon ER , SkolAD, PereraMA. The limits of genome-wide methods for pharmacogenomics. Pharmacogenet. Genomics, 22(4), 261–272 (2012).
   PubMed Web of Science ®Google Scholar
• Cavallari LH , ShinJ, PereraMA. Role of pharmacogenomics in the management of traditional and novel oral anticoagulants. Pharmacotherapy, 31(12), 1192–1207 (2011).
   PubMed Web of Science ®Google Scholar
• Guyatt GH , AklEA, CrowtherM, GuttermanDD, SchunemannHJ. Executive summary: antithrombotic therapy and prevention of thrombosis (9th Edition). American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 141(Suppl. 2), S7–S47 (2012).
   PubMed Web of Science ®Google Scholar
• Flockhart DA , O‘KaneD, WilliamsMSet al. Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genet. Med. , 10(2), 139–150 (2008).
   PubMed Web of Science ®Google Scholar
• Caraco Y , BlotnickS, MuszkatM. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin. Pharmacol. Ther., 83(3), 460–470 (2008).
   PubMed Web of Science ®Google Scholar
• Epstein RS , MoyerTP, AubertREet al. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo warfarin effectiveness study). J. Am. Coll. Cardiol. , 55(25), 2804–2812 (2010).
   PubMed Web of Science ®Google Scholar
• French B , JooJ, GellerNLet al. Statistical design of personalized medicine interventions: the Clarification of Optimal Anticoagulation through Genetics (COAG) trial. Trials , 11, 108 (2010).
   PubMed Web of Science ®Google Scholar
• Johnson JA , GongL, Whirl-CarrilloMet al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin. Pharmacol. Ther. , 90(4), 625–629 (2011).
   PubMed Web of Science ®Google Scholar
• Finkelman BS , GageBF, JohnsonJA, BrensingerCM, KimmelSE. Genetic warfarin dosing: tables versus algorithms. J. Am. Coll. Cardiol., 57(5), 612–618 (2011).
   PubMed Web of Science ®Google Scholar

Websites

• Warfarin dosing. www.warfarindosing.org
   Google Scholar
• Database of single nucleotide polymorphisms. Bethesda (MD): National Center for Biotechnology Information, National Library of Medicine. dbSNP accession: ss5586420, ss52052050, ss76884483, ss105439387, ss105440151, ss13761958, ss10622649, ss2494699, ss3027906 (dbSNP Build ID:132). www.ncbi.nlm.nih.gov/snp
   Google Scholar
• US Census Bureau. 1970, 1980, and 2000 decennial censuses: population projections, 1 July 2010–1 July 2050. www.census.gov
   Google Scholar