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 10 annotations for this variant. Register or sign in to see them.
VIP Variant in CYP2B6
The CYP2B6:1459C>T variant was first identified by Lang et al. in 2001[Article:11470993]. Found at 9-14% in Caucasians and 2-9% in Blacks or African Americans [Article:17638512], this variant has been reported to reduce CYP2B6 protein expression in human liver [Article:11470993] and brain [Article:12814665]. Human liver microsomes with the TT genotype had lower protein expression and reduced mephenytoin metabolism (n=92)[Article:11470993]. Other studies have had conflicting results but were limited by small numbers and lack of homozygotes [Article:14551287, 15083067]. Preliminary genotyping of a small sample set (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine [Article:12814665].
In vivo, 1459C>T was not associated with plasma concentrations of efavirenz or nevirapine [Article:18281305] or bupropion [Article:14515060]. In vivo studies of CYP2B6 and bupropion are however confounded by the interactions of CYP2B6 and nicotine and the potential differences between brain and liver CYP2B6 expression and activity. In a smoking cessation study with bupropion, individuals with the DRD2-Taq1 A2A2 genotype demonstrated higher odds of abstinence only if they possessed the CYP2B6 1459 TT or CT genotype [Article:17654295]. Some of this may be due to the fact that smokers with the CYP2B6 variant may be more vulnerable to abstinence symptoms and relapse. However it was also noted that bupropion may attenuate these effects, especially among females [Article:12439223]. CYP2B6:1459C>T has also been reported to have a small but significant effect on clearance of thiotepa or tepa [Article:19076156].
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Drug (1)
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| Diseases | Tobacco Use Disorder |
Appendix
| mRNA Variant & GenBank ID: | 1466C>T on NM_000767.4 |
|---|---|
| Protein Variant & GenBank ID: | Arg487Cys on NP_000758.1 |
| DNA Source Containing Homozygous Reference Allele (Coriell Lines): | CC Sample PA126746541 (NA17201) |
| DNA Source Containing Heterozygous Reference Allele (Coriell Lines): | CT Sample PA126746542 (NA17202) |
| DNA Source Containing Homozygous Minor Allele (Coriell Lines): | TT Sample PA126746543 (NA17203) |
Connected Drugs
| Evidence | Drug |
|---|---|
| bupropion | |
| cyclophosphamide | |
| doxorubicin | |
| efavirenz | |
| methadone | |
| nevirapine |
Connected Diseases
| Evidence | Disease |
|---|---|
| Breast Neoplasms | |
| Heroin Dependence | |
| HIV | |
| HIV Infections | |
| Tobacco Use Disorder |