rs3745274
This is a missense variant in the CYP2B6 gene.
Key Literature Trait Associations
Efavirenz Metabolism
CYP2B6*6 carries a Q172H substitution that reduces protein expression and catalytic activity. Homozygous *6/*6 carriers have 3-4 fold higher efavirenz plasma levels, significantly increasing risk of CNS side effects including dizziness, vivid dreams, and depression. CPIC recommends dose reduction to 400 mg (from standard 600 mg) or selection of an alternative antiretroviral for CYP2B6 poor metabolizers. This variant also affects methadone and bupropion metabolism.
▶ClinVar annotation
Efavirenz response; CYP2B6-related disorder; efavirenz response - Metabolism/PK; efavirenz response - Toxicity; nevirapine response - Metabolism/PK; Familial cancer of breast
View on ClinVar →▶Research that mentions this SNP (4)
▶Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancerAssociationN=145Haroun F. et al.(2015)· Cancer Chemotherapy and Pharmacology
This pharmacogenetic study examined three CYP2B6 polymorphisms (rs2279343, rs3211371, rs3745274) in 145 Lebanese breast cancer patients receiving cyclophosphamide (CP) chemotherapy. While no significant associations were found with hematological toxicity, homozygous CYP2B6 variant haplotypes were associated with significantly shorter time-to-recurrence in a subset of 38 patients with relapsed disease. However, results were limited by small sample size (only 3 homozygous mutant patients) and the authors concluded current evidence is insufficient to justify routine CYP2B6 genotyping for CP dosing or toxicity prediction.
▶ABCB1andABCC1variants associated with virological failure of first-line protease inhibitors antiretroviral regimens in Northeast Brazil patientsAssociationN=187Antonio V.C. Coelho et al.(2013)· The Journal of Clinical Pharmacology
This retrospective cohort study of 187 Brazilian HIV patients examined associations between seven SNPs in five pharmacokinetic genes and virological failure on first-line protease inhibitor-based antiretroviral therapy. Two variants were significantly associated with treatment failure: rs1045642 (ABCB1) and rs212091 (ABCC1), suggesting that genetic variation in drug transporter proteins influences treatment outcomes in this population.
▶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.
▶Limited use of interleukin 28B in the setting of response-guided treatment with detailed on-treatment virological monitoringReviewAlessandra Mangia et al.(2011)· Hepatology
This is a special issue of the Italian medical journal BeAdfiles (September 2012) dedicated to genetic conditioning in HIV and hepatitis virus infections. It reviews the major genetic polymorphisms that influence disease progression, treatment response, and drug toxicity in HIV and chronic hepatitis B and C infections, with particular emphasis on IL28B polymorphisms (rs809917 and others) predicting HCV treatment response to interferon-alpha and ribavirin therapy, and ITPA gene variants protecting against ribavirin-induced anemia. The issue also covers pharmacogenetic markers (CYP2B6, ABCB1, HLA-B*5701) and their clinical applications in antiretroviral therapy.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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