{{Rsnum
|rsid=2108622
|Gene=CYP4F2
|Chromosome=19
|position=15879621
|Orientation=plus
|ReferenceAllele=G
|MissenseAllele=A
|GMAF=0.2153
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=Warfarin (Coumadin®)
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=CYP4F2
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 60.7 | 32.1 | 7.1
| HCB | 58.8 | 39.0 | 2.2
| JPT | 63.4 | 26.8 | 9.8
| YRI | 90.5 | 8.8 | 0.7
| ASW | 80.7 | 19.3 | 0.0
| CHB | 58.8 | 39.0 | 2.2
| CHD | 55.0 | 40.4 | 4.6
| GIH | 30.7 | 50.5 | 18.8
| LWK | 81.8 | 17.3 | 0.9
| MEX | 56.1 | 42.1 | 1.8
| MKK | 62.8 | 34.6 | 2.6
| TSI | 47.1 | 38.2 | 14.7
| HapMapRevision=28
}}{{CPMC SNP
|link=https://cpmc.coriell.org/Sections/Results/Warfarin.aspx?PgId=222
}}[[rs2108622]] is a SNP in the cytochrome P450, family 4, subfamily F, polypeptide 2 [[CYP4F2]] gene.

{{PMID|18787519}} In the males rs2108622(G) was significantly higher in cerebral infarction patients (P = 0.025)

{{PMID|19207028}} A study of Italian patients concluded that [[rs2108622]](T;T) patients require 5.49 mg/day of [[warfarin]] versus 2.93 mg/day for (C;C) patients. Analysis of variance indicates that about 7% of mean weekly warfarin dose variance is explained by CYP4F2 genotype.

{{PMID Auto
|PMID=19300499
|Title=A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose.
|OA=1
}}
{{PMID Auto
|PMID=19097922
|Title=A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men.
}}

{{omim
|desc=COUMARIN RESISTANCE
|id=122700
|rsnum=2108622
}}

{{omim
|desc=CYTOCHROME P450, FAMILY 4, SUBFAMILY F, POLYPEPTIDE 2; CYP4F2
|id=604426
|rsnum=2108622
}}
{{PMID Auto GWAS
|PMID=19578179
|Trait=Acenocoumarol maintenance dosage
|Title=A genome-wide association study of acenocoumarol maintenance dosage
|RiskAllele=
|Pval=3E-10
|OR=NR
|ORtxt=NR
}}
{{PMID Auto
|PMID=19741565
|Title=Effects of CYP4F2 genetic polymorphisms and haplotypes on clinical outcomes in patients initiated on warfarin therapy
}}

{{PharmGKB
|RSID=rs2108622
|Name_s=CYP4F2: C>T (V433M)
|Gene_s=CYP4F2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:20182420
|Annotation=Risk or phenotype-associated allele: no allelic association. Phenotype: Improved pharmacogenetic algorithm-based warfarin dosing. Study size: 370. Study population/ethnicity: Self identified white, black, or &quot;intermediate&quot; Brazilians. Significance metric(s): p > 0.05. Type of association: PK.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165291903
}}

{{PMID|20182420}} A study of 370 Brazilian ("admixed") patients concludes that prospective CYP4F2 genotyping is of little value to these patients, presumably due to ethnic-based differences.

{{PMID Auto
|PMID=20555338
|Title=Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements
}}
{{PMID Auto GWAS
|PMID=20833655
|Trait=None
|Title=Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese
|RiskAllele=T
|Pval=3E-8
|OR=None
|ORtxt=None
}}

{{PharmGKB
|RSID=rs2108622
|Name_s=CYP4F2:V433M
|Gene_s=CYP4F2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:17341693; PubMed ID:18250228
|Annotation=This variant is found to have clinical impact on stable warfarin dose. Patients with 2 TT alleles were reported to require approximately 1 mg/day more warfarin than patients with 2 CC alleles. This variant affects enzyme acitivity and was shown to decrease 20-HETE production in a reconstituted recombinant protein system to approximately 60% of the wild-type enzyme.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA161149199
}}

{{PharmGKB
|RSID=rs2108622
|Name_s=
|Gene_s=CYP4F2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19300499; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose. (Initial Sample Size: 1,053 individuals; Replication Sample Size: 588 individuals); (Region: 19p13.12; Reported Gene(s): CYP4F2; Risk Allele: rs2108622-?); (p-value= 0.0000000003).This variant is associated with Warfarin maintenance dose.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164739915
}}

{{PharmGKB
|RSID=rs2108622
|Name_s=CYP4F2: V433M
|Gene_s=CYP4F2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19297519
|Annotation=An in-vitro study demonstrated that CYP4F2 is a vitamin K(1) oxidase and that carriers of the CYP4F2 V433M allele have a reduced capacity to metabolize vitamin K. Secondary, this variant causes a decrease in steady-state hepatic concentrations of the enzyme.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164920441
}}

{{PharmGKB
|RSID=rs2108622
|Name_s=CYP4F2:V433M
|Gene_s=CYP4F2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19270263
|Annotation=In a study of 100 white men with nonvalvular atrial fibrillation, the CYP4F2 rs2108622 (V433M) genotype significantly contributes to both early anticoagulant effect (international normalized ratio [INR]) (R2 = 0.14) and acenocoumarol dose requirements (R2 = 0.19). The V433M genotype had a gene dosage-dependent effect in decreasing plasma clotting factors in early drug response, with 433V homozygotes being the most sensitive. After initiation of therapy, the INR showed a gene significant dosage-dependent effect (P = .015), and 433V subjects needing 4 mg/week less than 433M carriers to achieve a steady anticoagulation (P = .043). The dose required to achieve a steady INR was also influenced by CYP4F2 genotype, similar to data reported for warfarin therapy. The CYP4F2 433M allele is reported to have decreased activity.
|Drugs=acenocoumarol
|Drug Classes=
|Diseases=Arteriosclerosis; Heart Diseases; Hemorrhage; Intracranial Hemorrhages; Myocardial Infarction; Peripheral Vascular Diseases; Pulmonary Embolism; Stroke; Thromboembolism; venous thromboembolism; Venous Thrombosis
|Curation Level=Curated
|PharmGKB Accession ID=PA165110361
}}

{{PharmGKB
|RSID=rs2108622
|Name_s=CYP4F2:V433M
|Gene_s=CYP4F2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19270263
|Annotation=Double homozygous VKORC1 1173T/T, CYP4F2 433Val/Val (n = 5) showed the highest INR (3.1; 2.0-4.7) and required the lowest acenocoumarol dose (11 &#177; 3 mg/week) The addition of the V433M genotype to the VKORC1 genotype raised the R2 from 8% to 14% for INR, and from 12% to 19% for acenocoumarol dose requirements.
|Drugs=acenocoumarol
|Drug Classes=
|Diseases=Arteriosclerosis; Heart Diseases; Hemorrhage; Intracranial Hemorrhages; Myocardial Infarction; Peripheral Vascular Diseases; Pulmonary Embolism; Stroke; Thromboembolism; venous thromboembolism; Venous Thrombosis
|Curation Level=Curated
|PharmGKB Accession ID=PA165110431
}}

{{PharmGKB
|RSID=rs2108622
|Name_s=CYP4F2 exon 11, c.1297G>A, mRNA 1347G>A, p.Val433Met
|Gene_s=CYP4F2
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19794411
|Annotation=Risk or phenotype-associated allele: A allele Phenotype: The A allele was not associated with variability in warfarin maintenance dose (p = 0.1270), however the combined effect of variants and age explained 26.6% of the overall interindividual in warfarin dose variability, with VKORC1 (rs9923231 A allele) accounting for 19.1%, CYP2C9 (rs1799853 T allele, or rs1057910 C allele) for 3.2%, EPHX1 (rs2292566 A allele) for 1.7%, CYP4F2 (rs2108622 C allele) gentoypes for 1.1%, and age for 1.5%. Study size: 283. Study population/ethnicity: Hospitalized Caucasian patients aged 75 years or older, recruited Sep 2002-Nov 2004 in Ivry, France, and Oct 2005-Mar 2008 from 14 French centers. Significance metric(s): mixed. Type of association: GN; PK.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165111646
}}
{{PMID Auto
|PMID=21084764
|Title=The influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian patients
}}
{{PMID Auto
|PMID=21127708
|Title=Genetic Variation of VKORC1 and CYP4F2 Genes Related to Warfarin Maintenance Dose in Patients with Myocardial Infarction
|OA=1
}}
{{PMID Auto
|PMID=21187935
|Title=Genes Involved in the Metabolism of Poly-Unsaturated Fatty-Acids (PUFA) and Risk for Crohn's Disease in Children &amp; Young Adults
|OA=1
}}

{{PMID Auto GWAS
|PMID=21729881
|Trait=None
|Title=Genome-wide association study identifies common variants associated with circulating vitamin E levels.
|RiskAllele=T
|Pval=1E-10
|OR=0.0300
|ORtxt=[0.01-0.05] unit increase
|OA=1
}}

{{PMID Auto
|PMID=22172097
|Title=CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects
}}

{{PMID Auto
|PMID=22192158
|Title=Influence of CYP4F2 genotype on warfarin dose requirement-a systematic review and meta-analysis
}}

{{PMID Auto
|PMID=22549502
|Title=Effects of CYP4F2 Gene Polymorphisms on Warfarin Clearance and Sensitivity in Korean Patients With Mechanical Cardiac Valves
}}

{{PMID Auto GWAS
|PMID=22437554
|Trait=None
|Title=Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men.
|RiskAllele=T
|Pval=2E-7
|OR=0.0400
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=18535201
|Title=A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose.
|OA=1
}}

{{PMID Auto
|PMID=18778477
|Title=Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival.
|OA=1
}}

{{PMID Auto
|PMID=18971550
|Title=Haplotype-based case-control study of the human CYP4F2 gene and essential hypertension in Japanese subjects.
}}

{{PMID Auto
|PMID=19955245
|Title=Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.
|OA=1
}}

{{PMID Auto
|PMID=19957603
|Title=[Association on the haplotypes of CYP4F2 gene and myocardial infarction].
}}

{{PMID Auto
|PMID=20149073
|Title=Pharmacogenetics of acenocoumarol in patients with extreme dose requirements.
}}

{{PMID Auto
|PMID=20227456
|Title=CYP4F2 gene V433M polymorphism is associated with ischemic stroke in the male Northern Chinese Han population.
}}

{{PMID Auto
|PMID=20377871
|Title=SNP-RFLPing 2: an updated and integrated PCR-RFLP tool for SNP genotyping.
|OA=1
}}

{{PMID Auto
|PMID=20538623
|Title=Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver.
|OA=1
}}

{{PMID Auto
|PMID=20585445
|Title=A novel, single algorithm approach to predict acenocoumarol dose based on CYP2C9 and VKORC1 allele variants.
|OA=1
}}

{{PMID Auto
|PMID=20653676
|Title=CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement.
|OA=1
}}

{{PMID Auto
|PMID=21228733
|Title=Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients.
|OA=1
}}

{{PMID Auto
|PMID=21562147
|Title=Identification of cytochrome P450 oxidoreductase gene variants that are significantly associated with the interindividual variations in warfarin maintenance dose.
|OA=1
}}

{{PMID Auto
|PMID=21625857
|Title=Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke.
}}

{{PMID Auto
|PMID=22010099
|Title=VKORC1 and CYP2C9 genotype and patient characteristics explain a large proportion of the variability in warfarin dose requirement among children.
}}

{{PMID Auto
|PMID=22486182
|Title=Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients.
}}

{{PMID Auto
|PMID=22528326
|Title=Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients.
}}

{{PMID Auto
|PMID=23013706
|Title=Correlation between single nucleotide polymorphisms in CYP4F2 and warfarin dosing in chinese valve replacement patients
|OA=1
}}

{{GET Evidence
|gene=CYP4F2
|aa_change=Val433Met
|aa_change_short=V433M
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=recessive
|quality_scores=Array
|dbsnp_id=rs2108622
|overall_frequency_n=2426
|overall_frequency_d=10758
|overall_frequency=0.225507
|n_genomes=17
|n_genomes_annotated=0
|n_haplomes=22
|n_articles=4
|n_articles_annotated=4
|in_gwas=Y
|in_pharmgkb=Y
|pph2_score=0.309
|nblosum100=0
|autoscore=2
|webscore=N
|summary_short=Requires 1mg/day greater dose of warfarin.
}}

{{PMID Auto
|PMID=23132553
|Title=Impact of the CYP4F2 p.V433M Polymorphism on Coumarin Dose Requirement: Systematic Review and Meta-Analysis
|OA=1
}}

{{PMID Auto
|PMID=23104259
|Title=Influence of warfarin dose-associated genotypes on the risk of hemorrhagic complications in Chinese patients on warfarin
}}

{{PMID Auto GWAS
  |PMID=23281178
  |Trait=Metabolite levels
  |Title=A genome-wide assessment of variability in human serum metabolism.
  |RiskAllele=T
  |Pval=9E-24
  |OR=NR
  |ORtxt=NR
  }}

{{PMID Auto
|PMID=22676711
|Title=Pharmacogenomics of warfarin in populations of African descent.
|OA=1
}}

{{PMID Auto
|PMID=22892446
|Title=Influence of CYP4F2 polymorphisms and plasma vitamin K levels on warfarin sensitivity in Japanese pediatric patients.
}}

{{PMID Auto
|PMID=23061746
|Title=Impact of genetic factors (CYP2C9, VKORC1 and CYP4F2) on warfarin dose requirement in the Turkish population.
}}

{{PMID Auto
|PMID=23691226
|Title=Novel associations of VKORC1 variants with higher acenocoumarol requirements.
|OA=1
}}

{{PMID Auto
|PMID=24896259
|Title=Genome at Juncture of Early Human Migration: A Systematic Analysis of Two Whole Genomes and Thirteen Exomes from Kuwaiti Population Subgroup of Inferred Saudi Arabian Tribe Ancestry
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}