rs1799853
badMag 7.0This is a protein-altering variant in the CYP2C9 gene.
Key Literature Trait Associations
Warfarin Sensitivity
CYP2C9*2 reduces warfarin metabolism by ~30%. Carriers require lower warfarin doses to achieve therapeutic anticoagulation. FDA-approved pharmacogenomic dosing guidelines incorporate this variant.
Siponimod metabolism
Siponimod (Mayzent), a sphingosine-1-phosphate receptor modulator approved for secondary progressive multiple sclerosis, is extensively metabolized by CYP2C9. A systematic review of siponimod pharmacogenetics found that CYP2C9*2 (rs1799853) is a relevant reduced-function allele, with *2/*3 compound heterozygotes considered poor metabolizers who are contraindicated from siponimod use. The review noted some heterogeneity in how *2 homozygotes are classified, recommending exclusion of pure *2/*2 carriers from initial prescribing caution unless *3 co-occurs, reflecting regulatory labeling guidance.
NSAID-induced gastrointestinal bleeding
CYP2C9*2 (rs1799853-T) reduces the hepatic clearance of CYP2C9-substrate NSAIDs such as diclofenac, ibuprofen, celecoxib, and meloxicam, leading to elevated plasma drug concentrations and prolonged drug exposure. A meta-analytic review concluded that carriers of CYP2C9*2 and *3 alleles have increased risk of acute gastrointestinal bleeding during NSAID use due to higher drug AUC and reduced elimination. This pharmacokinetic effect is consistent with the known 30–50% reduction in CYP2C9 activity conferred by the *2 allele.
Sulfonylurea response in type 2 diabetes mellitus
CYP2C9 is the principal enzyme metabolizing sulfonylureas (glibenclamide, glipizide, glimepiride, tolbutamide), and rs1799853-T (*2 allele) reduces metabolic clearance. A systematic review of 9,170 patients with type 2 diabetes found rs1799853 among the most commonly investigated CYP2C9 variants in sulfonylurea pharmacogenomics studies, with reduced-function alleles generally associated with altered glycemic response and risk of hypoglycemia. Results were heterogeneous across populations, reflecting differences in allele frequency and study design.
▶ClinVar annotation
Warfarin response; not specified; Lesinurad response; Flurbiprofen response; not provided; Piroxicam response; Phenytoin response
View on ClinVar →▶Research that mentions this SNP (4)
▶Genetic Variants Associated With Phenytoin-Related Severe Cutaneous Adverse ReactionsAssociationN=4,268Wen-Hung Chung et al.(2014)· JAMA
Genome-wide association study and replication analysis identified CYP2C gene variants, particularly the missense variant rs1057910 (CYP2C9*3, Ile359Leu), as strongly associated with phenytoin-related severe cutaneous adverse reactions (SJS/TEN/DRESS) across Taiwan, Japan, and Malaysia populations. The CYP2C9*3 variant showed an overall odds ratio of 11 (95% CI, 6.2-18; P < 0.00001) in meta-analysis of three populations and is known to reduce drug clearance. A cluster of 16 SNPs in CYP2C genes at 10q23.33 reached genome-wide significance.
▶Interindividual Variability in the Hepatic Expression of the Human Breast Cancer Resistance Protein (BCRP/ABCG2): Effect of Age, Sex, and GenotypeAssociationN=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.
▶VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest ChinaAssociationN=260Qiang Gu et al.(2010)· European Journal of Clinical Pharmacology
Study of 127 southwest Chinese Han patients with mechanical heart valve prostheses examined genetic polymorphisms in VKORC1 -1639G>A (rs9923231), CYP2C9 (*3: rs1057910, IVS3-65G>C: rs9332127), and EPHX1 691A>G (rs4653436) as predictors of warfarin maintenance dosage. A multiple linear regression model incorporating these genetic variants plus age and body weight explained 74.3% of interindividual variability in warfarin dosing, with VKORC1 -1639G>A being the strongest predictor (r=0.769, p<0.001).
▶Association of warfarin dose with genes involved in its action and metabolismAssociationN=201Mia Wadelius et al.(2007)· Human Genetics
An association study of 201 warfarin-treated patients found that polymorphisms in VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, and APOE were significantly associated with warfarin dose requirement (P < 0.000175 for VKORC1 and CYP2C9). A multiple regression model incorporating VKORC1, CYP2C9, PROC, and non-genetic factors (age, bodyweight, drug interactions, treatment indication) accounted for 62% of the variance in warfarin dose.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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