{{Rsnum
|rsid=1799853
|Gene=CYP2C9
|Chromosome=10
|position=94942290
|Orientation=plus
|ReferenceAllele=C
|MissenseAllele=T
|GMAF=0.06841
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=Warfarin (Coumadin®)
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=CYP2C9
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 81.0 | 19.0 | 0.0
| HCB | 100.0 | 0.0 | 0.0
| JPT | 100.0 | 0.0 | 0.0
| YRI | 100.0 | 0.0 | 0.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 100.0 | 0.0 | 0.0
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}{{CPMC SNP
|link=https://cpmc.coriell.org/Sections/Results/Warfarin.aspx?PgId=222
}}
rs1799853 is a SNP in the CYP2C9 gene and is linked to poor warfarin metabolism. Advanced knowledge of this may influence initial warfarin dosing by physicians. [[Warfarin]] is monitored through INR (international normalized ratio) and proper dosing is influenced by a variety of factors including warfarin metabolism and diet.
 {{PMID|1305837}}  
 
[[rs1799853]] is a SNP in the [[CYP2C9]] gene. The [[rs1799853]](T) allele encodes a variant amino acid, cysteine, which has been linked to poor metabolism of [[warfarin]] and thus sensitivity {{PMID|15608560}}. The common nomenclature for this polymorphism is CYP2C9*2 (Cys amino acid, T allele; the SNP is also known as C430T or Cys144Arg).

The effect of [[CYP2C9]] variants on drug metabolism should not be predicted without also considering [[CYP2C9*3]], defined as the common loss of function variant [[rs1057910]](C) [http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=1799853] (NM_000771:c.430C>T, NP_000762:p.144R>C) {{PMID|8004131}} [http://www.pharmgkb.org/search/annotatedGene/cyp2c9/].

Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of [[nonsteroidal anti-inflammatory drug]]s ([[NSAID]]s) that are CYP2C8 or CYP2C9 substrates, such as [[aceclofenac]], [[celecoxib]], [[diclofenac]], [[ibuprofen]], [[indomethazine]], [[lornoxicam]], [[meloxicam]], [[naproxen]], [[piroxicam]], [[tenoxicam]] and [[valdecoxib]].{{PMID|19422321}}

{{PMID Auto GWAS
|PMID=19300499
|Trait=Warfarin maintenance dose
|Title=A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose
|RiskAllele=
|Pval=1E-31
|OR=0.54
|ORtxt=[0.45-0.63] mg/week decrease
|OA=1
}}

{{PharmGKB
|RSID=rs1799853
|Name_s=CYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys
|Gene_s=CYP2C9
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19794411
|Annotation=Risk or phenotype-associated allele: rs1799853 T allele Phenotype: CYP2C9 wild-type (reference) allele carriers required a mean warfarin dose of 3.2 &#177; 1.6 mg, whereas patients carrying one or two CYP2C9 variant alleles (CYP2C9*2 = rs1799853 T allele, CYP2C9*3 = rs1057910 C allele, relative to CYP2C9*1 = reference) required significantly lower doses (*1/*x: 2.7 &#177; 1.5 mg (&#8722;16%); *x/*x: 1.9 &#177; 1.1 mg (&#8722;41%)) (p = 0.0015). CYP2C9 genotypes showed significant influence on the time to the first INR >=2 (p = 0.0016). The risk for having an INR value >=4 was higher in individuals with multiple variants of CYP2C9 or VKORC1 (rs9923231 A allele) (OR = 12.8, 95% CI = 2.73-60.0). The combined effect of variants and age, explained 26.6% of the variability in the warfarin dose, 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) 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): p < = 0.0016. Type of association: GN; PK.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165111644
}}

{{PMID Auto
|PMID=20214591
|Title=Pharmacogenomics in aspirin intolerance
}}
{{PMID Auto
|PMID=20555338
|Title=Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements
}}

{{PharmGKB
|RSID=rs1799853
|Name_s=CYP2C9*2; CYP2C9:144Arg>Cys
|Gene_s=CYP2C9
|Feature=Exon/NonSyn
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/cyp2c9/variant.jsp#ImportantVariantInformationforCYP2C9-111
|Annotation=This variant has been shown to influence warfarin dose as well as affecting the clearance of several other drugs.
|Drugs=fluvastatin; glipizide; phenytoin; tolbutamide; warfarin
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145194
}}

{{PharmGKB
|RSID=rs1799853
|Name_s=
|Gene_s=CYP2C9
|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: 10q23.33; Reported Gene(s): CYP2C9; Risk Allele: rs1799853-?); (p-value= 1E-31).This variant is associated with Warfarin maintenance dose.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164739916
}}

{{PharmGKB
|RSID=rs1799853
|Name_s=CYP2C9*2; CYP2C9:144Arg>Cys
|Gene_s=CYP2C9
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19228618
|Annotation=This variant (CYP2C9*2) has been shown to influence warfarin dose and is included in the pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA162652683
}}

{{PharmGKB
|RSID=rs1799853
|Name_s=CYP2C9*2, CYP2C9:Arg144Cys
|Gene_s=CYP2C9
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19794412
|Annotation=In a study of Scottish patients receiving sulfonylureas (n=1073), those with any CYP2C9*2 alleles were less likely to experience treatment failure, and CYP2C9*2 homozygotes had greater reductions in HbA(1c) than CYP2C9*1.
|Drugs=glibenclamide; gliclazide; glimepiride; glipizide
|Drug Classes=SULFONAMIDES, UREA DERIVATIVES
|Diseases=Diabetes Mellitus
|Curation Level=Curated
|PharmGKB Accession ID=PA165107375
}}

{{PharmGKB
|RSID=rs1799853
|Name_s=CYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys
|Gene_s=CYP2C9
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19794412
|Annotation=Risk or phenotype-associated allele: CYP2C9*2, rs1799853 T allele, Cys144. Phenotype: Drug response phenotypes included (1) reaching target HbA(1c), (2) maximum HbA(1c) reduction, and (3) time to monotherapy failure. Patients homozygous for the loss-of-function CYP2C9 alleles (*2/*2, *2/*3, *3/*3) achieved greater treatment target (OR = 3.4, p = 0.0009), 0.5% greater reduction in target HbA1c concentration (p = 0.003), and lower risk of monotherapy failure based an additive genetic model (allelic hazard ratio 0.79, 95% confidence interval 0.63-0.99, p = 0.04), compared to wild-type allele (*1) carriers. Study size: 1,073 patients (578 drug-naive, 495 with prior and continued metformin exposure). Study population/ethnicity: Diabetes patients recruited in Tayside, Scotland for the Diabetes Audit and Research Tayside Study (DARTS), between 1992 and 2007, who were incident sulfonylurea users. Significance metric(s): p = (0.04 - 0.0009) Type of association: GN; PD
|Drugs=glibenclamide; gliclazide; glimepiride; glipizide; metformin
|Drug Classes=SULFONAMIDES, UREA DERIVATIVES
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA165111640
}}

{{omim
|id=601130
|desc=CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 9; CYP2C9
|rsnum=1799853
}}
{{omim
|id=601130
|rsnum=1799853
|variant=0002
}}

{{PMID Auto
|PMID=22118051
|Title=Genetic variants in CYP (-1A2, -2C9, -2C19, -3A4 and -3A5), VKORC1 and ABCB1 genes in a black South African population: a window into diversity
}}

{{ClinVar
|rsid=1799853
|Reversed=0
|FwdREF=C
|FwdALT=T
|REF=C
|ALT=T
|RSPOS=96702047
|CHROM=10
|GMAF=0.0682
|dbSNPBuildID=89
|SSR=0
|SAO=1
|VP=0x050378000000150117130100
|GENEINFO=CYP2C9:1559
|GENE_NAME=CYP2C9
|GENE_ID=1559
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000010.10:g.96702047C>T
|CLNSRC=OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=601130.0002
|CLNSIG=255
|CLNCUI=CN078029
|CLNDBN=Warfarin response
|Disease=Warfarin response
|CLNACC=RCV000008920.1
|Tags=PM;TPA;PMC;S3D;SLO;VLD;G5;GNO;KGPhase1;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.9316; 0.06841
|CLNDSDB=MedGen:OMIM
|CLNDSDBID=CN078029:122700
|COMMON=1
}}

{{PMID|17048007|OA=1
}} Association of warfarin dose with genes involved in its action and metabolism.

{{PMID|17387222|OA=1
}} Genetic-based dosing in orthopedic patients beginning warfarin therapy.

{{PMID|18305455|OA=1
}} Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin.

{{PMID|18466099|OA=1
}} Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans.

{{PMID|18547414|OA=1
}} Genotyping panel for assessing response to cancer chemotherapy.

{{PMID|18574025|OA=1
}} The largest prospective warfarin-treated cohort supports genetic forecasting.

{{PMID|18596683|OA=1
}} Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

{{PMID|18662264|OA=1
}} Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients.

{{PMID|18680736}} Genetic factors contribute to patient-specific warfarin dose for Han Chinese.

{{PMID|18752379|OA=1
}} Warfarin pharmacogenetics.

{{PMID|18990750|OA=1
}} Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk.

{{PMID|18992148|OA=1
}} Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.

{{PMID|18992263|OA=1
}} Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways.

{{PMID|19223558|OA=1
}} Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma.

{{PMID|19538716|OA=1
}} Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).

{{PMID|19761371|OA=1
}} Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.

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

{{PMID|20082485|OA=1
}} Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

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

{{PMID|20459744|OA=1
}} Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.

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

{{PMID|20733952|OA=1
}} Warfarin genotyping using three different platforms.

{{PMID|20808793|OA=1
}} Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?

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

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

{{PMID|22569204|OA=1
}} PharmGKB summary: phenytoin pathway.

{{PMID Auto
|PMID=23081681
|Title=CYP2C9 variants increase risk of colorectal adenoma recurrence and modify associations with smoking but not aspirin treatment
|OA=1
}}

{{GET Evidence
|gene=CYP2C9
|aa_change=Arg144Cys
|aa_change_short=R144C
|impact=pharmacogenetic
|qualified_impact=Moderate clinical importance,  pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1799853
|overall_frequency_n=1044
|overall_frequency_d=10752
|overall_frequency=0.0970982
|n_genomes=5
|n_genomes_annotated=0
|n_haplomes=6
|n_articles=7
|n_articles_annotated=6
|qualityscore_in_silico=2
|qualitycomment_in_silico=Y
|qualityscore_in_vitro=3
|qualitycomment_in_vitro=Y
|qualityscore_case_control=4
|qualitycomment_case_control=Y
|qualityscore_severity=3
|qualitycomment_severity=Y
|qualityscore_treatability=3
|qualitycomment_treatability=Y
|in_omim=Y
|in_gwas=Y
|in_pharmgkb=Y
|pph2_score=0.954
|nblosum100=8
|autoscore=3
|webscore=N
|variant_evidence=1
|clinical_importance=2
|summary_short=This variant, also called CYP2C9*2, is a pharmacogenetic variant that modulates sensitivity for Warfarin (due to reduced metabolism). This variant is associated with Caucasians. The FDA has approved reduced recommended Warfarin dosage based on the presence of this variant.
}}

{{PMID Auto
|PMID=23473641
|Title=Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients
}}

{{PMID Auto
|PMID=23587916
|Title=Allele frequency distribution of CYP2C9 2 and CYP2C9 3 polymorphisms in six Mexican populations
}}

{{PMID Auto
|PMID=24324947
|Title=VKORC1 and CYP2C9 Genotype Variations in Relation to Warfarin Dosing in Korean Stroke Patients
|OA=1
}}

{{PMID Auto
|PMID=24368493
|Title=Interaction between ALOX5AP and CYP3A5 gene variants significantly increases the risk for cerebral infarctions in Chinese
}}

{{PMID Auto
|PMID=24380239
|Title=Characterization of the most common CYP2C9 and CYP2C19 allelic variants in the population from the Republic of Macedonia
}}

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

{{PMID Auto
|PMID=23130019
|Title=Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.
|OA=1
}}

{{PMID Auto
|PMID=23133420
|Title=Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
|OA=1
}}

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

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}