rs4244285
badMag 8.0This is a splice acceptor variant variant in the CYP2C19 gene.
Key Literature Trait Associations
Clopidogrel Response
The CYP2C19*2 allele is the most common loss-of-function variant, carried by ~25% of people. Poor metabolizers cannot efficiently convert clopidogrel (Plavix) to its active form, leading to reduced antiplatelet effect and increased cardiovascular event risk. FDA label includes a boxed warning about CYP2C19 poor metabolizers.
Ischemic stroke recurrence
Among ischemic stroke and TIA patients treated with clopidogrel, CYP2C19*2 (rs4244285) carriers have substantially elevated risk of stroke recurrence. A meta-analysis of 10 Chinese trials (1,333 patients) found that GA+AA genotypes conferred OR 2.50 (95% CI 1.66–3.75) for recurrence compared to GG, with homozygous AA carriers showing OR 4.40. Poor metabolisers had OR 3.32 versus extensive metabolisers. These findings support genotype-guided antiplatelet selection after stroke/TIA, particularly in East Asian populations where the *2 allele is more prevalent.
Antidepressant response
Poor metabolisers (homozygous CYP2C19*2 carriers) treated with citalopram or escitalopram show meaningfully improved symptom remission compared to extensive metabolisers (OR 1.55 for remission, SMD 0.43 for symptom improvement), reflecting higher drug plasma levels due to impaired CYP2C19-mediated clearance. However, they also experience significantly higher rates of gastrointestinal, neurological, and sexual side effects. The clinical impact is limited by the low frequency of true poor metabolisers (~2% of Europeans), but intermediate metabolisers (heterozygous *2 carriers, ~15–30% of most populations) also show intermediate phenotypes.
Endometriosis
A systematic review and meta-analysis of genetic polymorphisms in endometriosis found a significant trend towards association between CYP2C19 rs4244285 and endometriosis risk, potentially reflecting CYP2C19's role in oestrogen metabolism. However, no definitive odds ratio was established for rs4244285 specifically, and the authors called for further dedicated studies. Evidence remains preliminary and this association should not be considered clinically actionable at present.
Breast cancer
A 2026 meta-analysis of CYP2C19 genetic variants and breast cancer susceptibility found that the GG (wild-type) genotype of rs4244285 showed a potential protective effect against breast cancer, implying that the A allele may marginally increase risk. However, most models in the analysis found no statistically significant association, and the effect is not established as clinically meaningful. CYP2C19's role in oestrogen metabolism provides biological plausibility, but this association requires replication in larger, well-powered studies.
▶ClinVar annotation
▶Research that mentions this SNP (7)
▶CYP2C19 genotype–phenotype discordance in patients with multiple myeloma leads to an acquired loss of drug-metabolising activityFunctionalN=25Burns KE et al.(2014)· Cancer Chemotherapy and Pharmacology
Study of 25 multiple myeloma patients examined CYP2C19 genotype-phenotype discordance using three common variants (rs4244285, rs49486893, rs12248560). Despite no homozygous null genotypes, 28% of patients showed poor metabolizer phenotype measured by proguanil metabolic ratio, indicating acquired loss of CYP2C19 activity independent of genetic variation (p < 0.0001). Discordance did not correlate with inflammatory markers CRP or IL-6.
▶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.
▶A candidate gene study of serotonergic pathway genes and pain relief during treatment with escitalopram in patients with neuropathic pain shows significant association to serotonin receptor2C (HTR2C)AssociationN=34Charlotte Brasch-Andersen et al.(2011)· European Journal of Clinical Pharmacology
A candidate gene study of 34 patients with neuropathic pain found significant association between the serotonin receptor 2C gene (HTR2C rs6318 C allele) and pain relief during escitalopram treatment, with an odds ratio of 15.5 (p=0.014) in men and 10.6 (p=0.010) in combined analysis. Additional genes in the serotonergic pathway including HTR2A, SLC6A4 (5-HTTLPR), CYP2C19, and ABCB1 were also analyzed, with 5-HTTLPR showing a borderline association.
▶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.
▶Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai womenAssociationN=200Suleeporn Sangrajrang et al.(2009)· International Journal of Cancer
This case-control association study of 200 breast cancer patients examined the relationship between CYP2C19*2 (rs4244285, G681A) and CYP17 (rs743572, T34C) polymorphisms and chemotherapy-induced toxicities. CYP2C19*2 variant genotype showed significant associations with adriamycin-induced hematological toxicities (anemia OR=9.77, neutropenia OR=5.72, febrile neutropenia OR=4.29, thrombocytopenia OR=5.86) and non-hematological toxicities (CINV OR=99.73, fatigue OR=83.29, peripheral neuropathy OR=12.00). CYP17 polymorphism showed significant association with paclitaxel-induced bodyache (OR=2.77) and peripheral neuropathy (OR=3.90).
▶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 Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel TherapyAssociationN=656Shuldiner AR et al.(2009)· JAMA
This genome-wide association study identified the CYP2C19*2 loss-of-function variant (rs4244285) as a major determinant of clopidogrel response in 429 Amish individuals. The variant was associated with diminished platelet aggregation response to ADP stimulation (P=4.3×10⁻¹¹) and accounted for 12% of variation in clopidogrel response. In an independent cohort of 227 patients undergoing percutaneous coronary intervention, carriers of CYP2C19*2 had higher cardiovascular event rates (20.9% vs 10.0%, HR=2.42, P=.02).
Gene information from NCBI Gene. Variant classifications from ClinVar.
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