Variant Annotations
PharmGKB variant annotations provide information about variant-drug pairs based on individual PubMed
publications. Each annotation represents information from a single paper and the goal is to report the
information that the author states, not an interpretation of the paper. The PMID for supporting PubMed
publications is found in the "Evidence" field.
Information presented, including study size, allele frequencies and statistics is taken directly from the
publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators
may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of
participants used for the calculation of the association statistics, so the number may vary slightly
from what is reported in the abstract of the paper. OMB Race Category information is derived from the
paper and mapped to standardized categories. Category definitions may be found by clicking on the
"OMB Race Category" link.
There are 29 annotations for this variant.
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There are 2 disease-related annotations for this variant.
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VIP Variant
in CYP2B6
The CYP2B6:516G>T variant was first reported to be associated with a slight but not significant reduction in hepatic CYP2B6 protein expression and activity [Article:11470993]. It is present in several haplotypes including the important haplotype, CYP2B6*6. This variant occurs more frequently in Blacks and African Americans as compared to Caucasians [Article:15622315]. Further study has shown impact of this variant on CYP2B6-mediated metabolism of non-nucleoside reverse transcriptase inhibitors (NNRTIs) [Article:15825040], although other studies with smaller samples sizes failed to show an effect [Article:16912956, 16912957]. The 516T variant has been associated with higher plasma exposure to efavirenz and may contribute towards efavirenz-associated central nervous system side effects [Article:15622315]. Conversely, the homozygous 516G variant results in sub-therapeutic plasma concentrations of efavirenz [Article:15825040, 18839779]. TT genotype for 516 has recently been associated with efavirenz pharmacokinetics as well as psychiatric side effects [Article:19531981, 19474465]. Recent studies have indicated that efavirenz dose modification for haplotypes including the 516G>T genotype may reduce side effects in adults [Article:17918089] and prevent subtherapeutic concentrations in children [Article:18839779]. In a recent study the composite CYP2B6:516G>T/983T>C genotype was significantly associated with plasma drug exposure and clearance for efavirenz but not nevirapine [Article:19239339]. However, larger prospective studies are needed to validate this association. In a recent study the composite CYP2B6:516G>T/983T>C genotype was significantly associated with plasma drug exposure and clearance for efavirenz but not nevirapine [Article:19239339].
Additionally, 516G>T has been associated with aberrant splicing of CYP2B6 (for more details see CYP2B6:SV1 [Article:18171905, 14551287].
| Key Publications: |
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| Drugs / Other Molecules |
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| Diseases |
HIV
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Appendix
| mRNA Variant & GenBank ID: | 523G>T on NM_000767.4 |
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| Protein Variant & GenBank ID: | Gln172His on NP_000758.1 |
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| DNA Source Containing Homozygous Reference Allele (Coriell Lines): | GG Sample PA126746542 (NA17202) |
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| DNA Source Containing Heterozygous Reference Allele (Coriell Lines): | GT Sample PA126746541 (NA17201) |
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| DNA Source Containing Homozygous Minor Allele (Coriell Lines): | TT Sample PA126746577 (NA17237)
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Publications related to rs3745274 at chr19:41512841: 26
The following icons indicate that data of a certain type is available:
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DG
Dosing Guideline information is available
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DL
Drug Label information is available
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CA
High-level Clinical Annotation is available
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VA
Variant Annotation is available
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VIP
VIP information is available
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PW
Pathway is available
[ close ]
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Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians. Pharmacogenomics. 2012. Brown Kevin C, et al. [Article:22111602@PubMed] |
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Associations Between ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 Alleles in Relation to Efavirenz and Nevirapine Pharmacokinetics in HIV-Infected Individuals. Therapeutic drug monitoring. 2012. Heil Sandra G, et al. [Article:22354160@PubMed] |
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Pharmacogenetics of toxicity, plasma trough concentration and treatment outcome with nevirapine-containing regimen in anti-retroviral-naïve HIV-infected adults: an exploratory study of the TRIANON ANRS 081 trial. Basic & clinical pharmacology & toxicology. 2011. Gozalo Claire, et al. [Article:21824325@PubMed] |
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Integration of absorption, distribution, metabolism, and elimination genotyping data into a population pharmacokinetic analysis of nevirapine. Pharmacogenetics and genomics. 2011. Lehr Thorsten, et al. [Article:21860339@PubMed] |
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Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients. Pharmacogenomics. 2011. Hung Chin-Chuan, et al. [Article:21902500@PubMed] |
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Factors influencing plasma nevirapine levels: a study in HIV-infected children on generic antiretroviral treatment in India. The Journal of antimicrobial chemotherapy. 2011. Swaminathan Soumya, et al. [Article:21393201@PubMed] |
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Integration of population pharmacokinetics and pharmacogenetics: an aid to optimal nevirapine dose selection in HIV-infected individuals. The Journal of antimicrobial chemotherapy. 2011. Schipani Alessandro, et al. [Article:21441248@PubMed] |
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Presence of the CYP2B6 516G> T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients. AIDS research and therapy. 2010. Gounden Verena, et al. [Article:20723261@PubMed] |
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Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. British journal of cancer. 2010. Bray J, et al. [Article:20179710@PubMed] |
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Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients. Pharmacogenomics. 2010. Elens Laure, et al. [Article:20860463@PubMed] |
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CYP2B6, CYP2A6 and UGT2B7 genetic polymorphisms are predictors of efavirenz mid-dose concentration in HIV-infected patients. AIDS (London, England). 2009. Kwara Awewura, et al. [Article:19779319@PubMed] |
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CYP2B6 (c.516G-->T) and CYP2A6 (*9B and/or *17) polymorphisms are independent predictors of efavirenz plasma concentrations in HIV-infected patients. British journal of clinical pharmacology. 2009. Kwara Awewura, et al. [Article:19371316@PubMed] |
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Cytochrome P450 2B6 516G-->T is associated with plasma concentrations of nevirapine at both 200 mg twice daily and 400 mg once daily in an ethnically diverse population. HIV medicine. 2009. Mahungu Tw, et al. [Article:19228205@PubMed] |
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Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2009. Rocha V, et al. [Article:19005482@PubMed] |
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Associations between CYP2B6 polymorphisms and pharmacokinetics after a single dose of nevirapine or efavirenz in African americans. The Journal of infectious diseases. 2009. Haas David W, et al. [Article:19239339@PubMed] |
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A pharmacokinetic and pharmacogenetic study of efavirenz in children: dosing guidelines can result in subtherapeutic concentrations. Antiviral therapy. 2008. ter Heine Rob, et al. [Article:18839779@PubMed] |
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Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. The Journal of antimicrobial chemotherapy. 2008. Wyen Christoph, et al. [Article:18281305@PubMed] |
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Aberrant splicing caused by single nucleotide polymorphism c.516G>T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver. The Journal of pharmacology and experimental therapeutics. 2008. Hofmann Marco H, et al. [Article:18171905@PubMed] |
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Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2007. Gatanaga Hiroyuki, et al. [Article:17918089@PubMed] |
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Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor hepatotoxicity. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2006. Ritchie Marylyn D, et al. [Article:16912956@PubMed] |
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Pharmacogenetics of nevirapine-associated hepatotoxicity: an Adult AIDS Clinical Trials Group collaboration. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2006. Haas David W, et al. [Article:16912957@PubMed] |
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Influence of 516G>T polymorphisms at the gene encoding the CYP450-2B6 isoenzyme on efavirenz plasma concentrations in HIV-infected subjects. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2005. Rodriguez-Novoa Sonia, et al. [Article:15825040@PubMed] |
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Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenetics and genomics. 2005. Rotger Margalida, et al. [Article:15864119@PubMed] |
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Pharmacogenetics of long-term responses to antiretroviral regimens containing Efavirenz and/or Nelfinavir: an Adult Aids Clinical Trials Group Study. The Journal of infectious diseases. 2005. Haas David W, et al. [Article:16267764@PubMed] |
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Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS (London, England). 2004. Haas David W, et al. [Article:15622315@PubMed] |
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Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. 2001. Lang T, et al. [Article:11470993@PubMed] |
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