rs1065852
This is a missense variant in the CYP2D6 gene.
Key Literature Trait Associations
Drug Metabolism (CYP2D6)
rs1065852 is the defining variant of CYP2D6*10 (c.100C>T, P34S), the most common reduced-function allele worldwide and especially prevalent in East Asian populations (allele frequency 40-70%). The Pro34Ser substitution destabilizes the CYP2D6 protein, reducing enzymatic activity to approximately 20-50% of normal. Carriers have decreased metabolism of CYP2D6 substrates including codeine, tramadol, tamoxifen, and many antidepressants.
Codeine Response
CYP2D6*10 carries a P34S substitution that destabilizes the enzyme, reducing its catalytic activity. It is the most common CYP2D6 variant in East Asian populations (~40% allele frequency), explaining the higher proportion of intermediate metabolizers in these populations. Carriers have reduced metabolism of codeine, tamoxifen, and many antidepressants, potentially requiring dose adjustments.
▶ClinVar annotation
Debrisoquine, poor metabolism of; Tramadol response; Deutetrabenazine response; Tamoxifen response; not provided; not specified
View on ClinVar →▶Research that mentions this SNP (4)
▶Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's diseaseReviewRenato Scacchi et al.(2014)· International Journal of Geriatric Psychiatry
This is a comprehensive review of genetic and biological determinants of acetylcholinesterase inhibitor (ChEI) response in Alzheimer's disease and other neurodegenerative diseases. The paper discusses how genetic variants in APOE (particularly the ε4 allele, which increases LOAD risk 3-15-fold), cholinergic system genes (CHRNA7, CHRFAM7A), and drug-metabolizing enzymes (CYP2D6, CYP3A4) influence both cholinergic homeostasis and clinical response to ChEI therapy, with emphasis on precision medicine approaches for patient stratification.
▶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 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.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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