rs28371725

This is a intronic variant in the CYP2D6 gene.

Key Literature Trait Associations

Codeine Response

CYP2D6*41 is an intronic variant that causes aberrant splicing and reduced mRNA expression, resulting in decreased CYP2D6 enzyme levels. CPIC classifies *41 as a decreased-function allele. It is common in Middle Eastern and European populations, and carriers may have reduced activation of codeine and tramadol and altered metabolism of tamoxifen and antidepressants.

Gierach M et al. Insulin resistance and thyroid disorders. Endokrynologia Polska 65(1):70-76 (2014)
Allele A
OR
p
Major Consortium Study

ClinVar annotation

Drug Response★★★
4 submitters37 publications

Deutetrabenazine response; Tamoxifen response; Tramadol response

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Research that mentions this SNP (4)

Interindividual Variability in the Hepatic Expression of the Human Breast Cancer Resistance Protein (BCRP/ABCG2): Effect of Age, Sex, and Genotype
AssociationN=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.

Traits studied:Drug-resistant epilepsyDrug-responsive epilepsyEpilepsyImatinib response in chronic myelogenous leukemiaPraziquantel responseTacrolimus metabolism
Association of RANBP1 haplotype with smooth pursuit eye movement abnormality
ReviewHyun Sub Cheong et al.(2011)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

Traits studied:Alzheimer diseaseAntipsychotic drug responseAntipsychotic drug side effectsAnxiety disordersBipolar disorderCNS disordersDepressive disorderParkinson's diseasePsychotic disordersSchizoaffective disorderSchizophreniaTardive dyskinesiaVascular dementia
Influence of neurexin 1 (NRXN1) polymorphisms in clozapine response
ReviewRenan 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.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia
Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects
ReviewRenan 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.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia

Gene information from NCBI Gene. Variant classifications from ClinVar.

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