Clinical Annotation for CYP2B6*1, CYP2B6*6; cotinine or nicotine; Tobacco Use Disorder (level 3 Metabolism/PK)
Level of Evidence
Phenotype Category
Genes
Haplotypes
Drugs
Phenotypes
PharmGKB ID
| Allele | Phenotype |
|---|---|
| *1/ Function not assigned More allele information | Patients with the *1/ |
| *1/ Function not assigned More allele information | Patients with the *1/ |
Level of Evidence Calculation More information
- Total Score
- 2.125
- Score Breakdown
- Variant Annotations = 2.125
- Dosing Guideline Annotations = 0
- Drug Label Annotations = 0
- Level Modifiers
- Calculated Level from Score
- Level 3Learn more about Clinical Annotation Levels of Evidence(opens in new window)
Evidence
- 0 Dosing Guideline Annotations
- 0 Drug Label Annotations
- 2 Variant Annotations from 2 Publications
- 2 Positive association Variant Annotations
- 0 Negative association Variant Annotations
1. Annotation of CYP2B6 haplotypes CYP2B6*1CYP2B6*6
CYP2B6 *1/*6 is associated with increased clearance of cotinine and nicotine in healthy individuals as compared to CYP2B6 *1/*1.
Finding was significant across the total study cohort and in a subset of CYP2A6 "decreased metabolizers" (i.e. participants carrying at least one copy of the CYP2A6*2, *4, *7, *9 or *12 alelles) but lost significance in the subset of CYP2A6 normal metabolizers.
From Publication
Gene
Phenotype Category
Association Significance
PharmGKB ID
Score More info on scoring
Study Parameters
1.
Study type
Study size
Association p-value
Biogeographical group More info on groups
Population description
Study Cohort: P-value given for association of *1/*6 genotype and increase cotinine clearance in CYP2A6 decreased metabolizers.
2.
Study type
Study size
Association p-value
Biogeographical group More info on groups
Population description
Study Cohort: P-value given for association of *1/*6 genotype and increase nicotine clearance in CYP2A6 decreased metabolizers.
3.
Study type
Study size
Association p-value
Allele frequency
Biogeographical group More info on groups
Population description
Study Cohort: P-value given for association of *1/*6 genotype and increase nicotine clearance across all CYP2A6 phenotype groups.
4.
Study type
Study size
Association p-value
Allele frequency
Biogeographical group More info on groups
Population description
Study Cohort: P-value given for association of *1/*6 genotype and increase cotinine clearance across all CYP2A6 phenotype groups.
5.
Study type
Study size
Association p-value
Biogeographical group More info on groups
Population description
Study Cohort: P-value given for association of *1/*6 genotype and increase nicotine clearance in CYP2A6 normal metabolizers.
6.
Study type
Study size
Association p-value
Biogeographical group More info on groups
Population description
Study Cohort: P-value given for association of *1/*6 genotype and increase cotinine clearance in CYP2A6 normal metabolizers.
2. Annotation of CYP2B6 haplotypes CYP2B6*1CYP2B6*6
CYP2B6 *6 is associated with decreased metabolism of nicotine as compared to CYP2B6 *1.
In vitro study which looked at metabolism of nicotine to nicotine iminium and nornicotine.