rs1057910
This is a missense variant in the CYP2C9 gene.
Key Literature Trait Associations
Warfarin Sensitivity
CYP2C9*3 (I359L) reduces warfarin metabolism by approximately 80%, more severely than the *2 allele. Carriers typically require 30-50% lower warfarin doses to maintain therapeutic INR. This variant also significantly affects metabolism of phenytoin, celecoxib, and flurbiprofen. CPIC guidelines recommend reduced initial warfarin dosing for *3 carriers.
▶ClinVar annotation
Tolbutamide response; Warfarin response; Phenytoin response; Glipizide response; Flurbiprofen response; Piroxicam response; not provided; Lesinurad response
View on ClinVar →▶Research that mentions this SNP (7)
▶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.
▶Influence of ORM1 polymorphisms on the maintenance stable warfarin dosageAssociationN=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.
▶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).
▶Influence of neurexin 1 (NRXN1) polymorphisms in clozapine responseReviewRenan P. Souza et al.(2010)· Human Psychopharmacology: Clinical and Experimental
This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.
▶Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjectsReviewRenan P. Souza et al.(2009)· Human Psychopharmacology: Clinical and Experimental
A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.
▶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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