rs2108622

This is a missense variant in the CYP4F2 gene.

Key Literature Trait Associations

Warfarin Dose Requirement

CYP4F2*3 (V433M) reduces vitamin K1 hydroxylase activity, leading to higher hepatic vitamin K levels and increased warfarin dose requirements of approximately 1 mg/day per allele. This variant is included in the IWPC (International Warfarin Pharmacogenetics Consortium) dosing algorithm and is mentioned on the FDA warfarin label. CYP4F2 genotyping alongside CYP2C9 and VKORC1 improves warfarin dose prediction accuracy.

Caldwell MD et al. “CYP4F2 genetic variant alters required warfarin dose.” Blood (2008)
Allele T
OR —
β 0.740
p 5.2e-6
Preliminary work
Klein TE et al. “Estimation of the warfarin dose with clinical and pharmacogenetic data.” The New England Journal of Medicine 360(8):753-764 (2009)
Allele T
OR —
p —
Candidate gene study
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GWAS Catalog Trait Associations (23)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

hexadecanedioate measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.24
p 3.0e-108
N 14,296
Large GWAS
European

metabolite measurement

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.34
p 2.0e-92
N 7,897
Large GWAS
European
Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele T
OR 0.31
p 2.0e-11
N 2,532
Large GWAS
European
Mun-Gwan Hong et al. “A Genome-Wide Assessment of Variability in Human Serum Metabolism” Human Mutation (2013)
Allele T
OR —
p 9.0e-24
N 402
Small GWAS
European

gamma-CEHC measurement

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.30
p 5.0e-76
N 8,258
Large GWAS
European
Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)
Allele T
OR 0.28
p 2.0e-62
N 8,809
Large GWAS
European
Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)
Allele T
OR 0.29
p 2.0e-37
N 6,136
Large GWAS
European

X-11538 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.19
p 9.0e-66
N 14,296
Large GWAS
European

alpha-CEHC glucuronide measurement

Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)
Allele T
OR 0.39
p 3.0e-52
N 4,889
Large GWAS
European

octadecanedioylcarnitine (C18-DC) measurement

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.18
p 7.0e-28
N 8,049
Large GWAS
European

gamma-CEHC glucuronide measurement

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.21
p 5.0e-27
N 6,305
Large GWAS
European

tetradecanedioate measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)
Allele T
OR 0.11
p 4.0e-25
N 14,296
Large GWAS
European

octadecadienedioate (C18:2-DC) measurement

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)
Allele T
OR 0.17
p 1.0e-24
N 8,231
Large GWAS
European
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ClinVar annotation

Drug Response★★★★
3 submitters81 publications

warfarin response - Dosage; acenocoumarol response - Dosage; not provided; CYP4F2-related disorder

View on ClinVar →
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Research that mentions this SNP (3)

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A Genome-Wide Assessment of Variability in Human Serum Metabolism
AssociationN=891Mun-Gwan Hong et al.(2013)· Human Mutation

A genome-wide association study (GWAS) of serum metabolic quantitative trait loci (mQTLs) in 891 Swedish men identified seven replicating loci (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with variants showing significant associations with metabolite levels (P = 10^-13 to 10^-91). rs4345897:A>G in PYROXD2 showed the strongest association with caprolactam (P = 2.40 × 10^-91), while rs174549:A>G in FADS1 associated with glycerolphosphocholine (P = 1.91 × 10^-30). Pathway analysis implicated genes with acyl-CoA dehydrogenase activity (ACADS, ACADM, ACAD8, ACAD10, ACAD11, ACOXL) and mQTL SNPs were enriched across GWAS catalog regions.

Traits studied:BilirubinButyrylcarnitineCaprolactamDimethylheptanoylcarnitineGlycerolphosphocholineGlycochenodeoxycholic acidHexanoylcarnitineSerum metabolitesStearoylcarnitine
PubMedDOIMetascience Observatory
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Interindividual Variability in the Hepatic Expression of the Human Breast Cancer Resistance Protein (BCRP/ABCG2): Effect of Age, Sex, and Genotype
AssociationN=1,000Bhagwat Prasad et al.(2013)· Journal of Pharmaceutical Sciences

Case-control study of 1,000 Han Chinese individuals (450 epilepsy cases, 550 controls) examining associations between STX1B polymorphisms and epilepsy treatment response. The rs140820592 variant showed significant association with reduced epilepsy risk (OR=0.542, p=0.004) and drug-resistant epilepsy risk (OR=0.260, p=0.004), with eQTL analysis confirming rs140820592 regulates STX1B expression in brain tissues.

Traits studied:Drug-resistant epilepsyDrug-responsive epilepsyEpilepsyImatinib response in chronic myelogenous leukemiaPraziquantel responseTacrolimus metabolism
PubMedDOIMetascience Observatory
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Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage
AssociationN=191Lian Sheng Wang et al.(2013)· European Journal of Clinical Pharmacology

This study examined 191 Chinese patients on warfarin therapy to determine whether the ORM1 rs17650 polymorphism influences warfarin maintenance dosage. Results showed that warfarin dose was significantly correlated with VKORC1 rs7294, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms (all P<0.05), with these three genes explaining 24% of dosage variation. ORM1 *S/*S and *F1/*S carriers required approximately 10-17% lower warfarin doses compared to wild-type *F1/*F1 patients.

Traits studied:Warfarin anticoagulation responseWarfarin maintenance dosage
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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