rs3892097
| Orientation | minus |
| Stabilized | minus |
| Geno | Mag | Summary |
|---|---|---|
| (A;A) | 3 | CYP2D6 poor metabolizer; many associations related to drug metabolism |
| (A;G) | extensive metabolizer (usually) | |
| (G;G) | 0 | extensive metabolizer |
| Reference | GRCh38 38.1/142 |
| Chromosome | 22 |
| Position | 42128945 |
| Gene | CYP2D6, LOC102723722, LOC107987465, LOC107987481 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs3892097 |
| dbSNP (classic) | rs3892097 |
| ClinGen | rs3892097 |
| ebi | rs3892097 |
| HLI | rs3892097 |
| Exac | rs3892097 |
| Gnomad | rs3892097 |
| Varsome | rs3892097 |
| LitVar | rs3892097 |
| Map | rs3892097 |
| PheGenI | rs3892097 |
| Biobank | rs3892097 |
| 1000 genomes | rs3892097 |
| hgdp | rs3892097 |
| ensembl | rs3892097 |
| geneview | rs3892097 |
| scholar | rs3892097 |
| rs3892097 | |
| pharmgkb | rs3892097 |
| gwascentral | rs3892097 |
| openSNP | rs3892097 |
| 23andMe | rs3892097 |
| SNPshot | rs3892097 |
| SNPdbe | rs3892097 |
| MSV3d | rs3892097 |
| GWAS Ctlg | rs3892097 |
| Merged from | Rs1800716 |
| GMAF | 0.1061 |
| Max Magnitude | 3 |
Also known as c.506-1G>A or 1846G>A, the normal (or wild type) form of this SNP is a (G) as defined on the reverse/minus strand. The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6.
If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine [PMID 2211621] is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug.
The CYP2D6*4 allele (i.e. rs3892097(A)) has been postulated by researchers over the years to have many potential consequences, both positive and negative.
On the positive side: this allele may reduce the risk of certain cancers, such as bladder and lung [PMID 1978251], and it may correlate with somwhat less severe neurodegeneration in Alzheimer's [PMID 7574463].
On the other hand, at least two studies [PMID 14991823, PMID 15174030] have concluded that the risk of developing Parkinson's disease upon exposure to pesticides is increased from 3 to 8 fold among carriers of CYP2D6*4 alleles. The risk to CYP2D6*4 carriers appears proportional to the degree of pesticide exposure, with no additional risk of developing Parkinson's seen for CYP2D6*4 carriers with no pesticide exposure, and the highest increased risk of developing Parkinson's seen for CYP2D6*4 carriers with frequent exposure to pesticides.
Patients prescribed tricyclic antidepressants (TCA) who are homozygous for the CYP2D6*4 allele metabolize these drugs more slowly, which puts them at higher risk for adverse side effects. A study of ~1100 Dutch patients reports: (1) 6 fold more side effects upon switching antidepressants for CYP2D6*4 homozygotes, but not for heterozygotes, and (2) that the effective and maintenance doses of antidepressants for CYP2D6*4 homozygotes are lower than for patients with one or more higher metabolizing CYP2D6 alleles. [PMID 18070221
]
rs3892097(A;A) patients taking a beta blocker drug such as metoprolol are at ~4x increased risk for bradycardia, based on a study of 1,533 patients in the Rotterdam Study. These CYP2D6 *4/*4 homozygotes have the 'poor metabolizer' (PM) phenotypes, and had adjusted heart rates that were 8.5 beats/min lower compared with *1/*1 extensive metabolizers (EMs) (p < 0.001), leading to an increased risk of bradycardia in PMs (odds ratio of 3.86, CI: 1.68-8.86, p = 0.0014).[PMID 18784654]
[PMID 18547414] Genotyping panel for assessing response to cancer chemotherapy.
[PMID 19537956] CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women.
[PMID 20174590] Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms.
[PMID 20459744] Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.
[PMID 21840870] Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.
[PMID 22638694] CYP2D6 genotyping and use of antidepressants in breast cancer patients: test development for clinical application.
[PMID 22688145] Clinical response and side effects of metoclopramide: associations with clinical, demographic, and pharmacogenetic parameters
[PMID 23130019] Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.
[PMID 23133420] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
| ClinVar | |
|---|---|
| Risk | Rs3892097(A;A) |
| Alt | Rs3892097(A;A) |
| Reference | Rs3892097(G;G) |
| Significance | Other |
| Disease | Debrisoquine doxepin response - Dosage antidepressants response - Dosage trimipramine response - Dosage imipramine response - Dosage clomipramine response - Dosage tamoxifen response - Efficacy amitriptyline response - Dosage nortriptyline response - Dosage desipramine response - Dosage not provided |
| Variation | info |
| Gene | CYP2D6 |
| CLNDBN | Debrisoquine, poor metabolism of doxepin response - Dosage, Toxicity/ADR antidepressants response - Dosage, Toxicity/ADR trimipramine response - Dosage, Toxicity/ADR imipramine response - Dosage, Toxicity/ADR clomipramine response - Dosage, Toxicity/ADR tamoxifen response - Efficacy, Toxicity/ADR amitriptyline response - Dosage, Toxicity/ADR nortriptyline response - Dosage, Toxicity/ADR desipramine response - Dosage, Toxicity/ADR not provided |
| Reversed | 1 |
| HGVS | NC_000022.10:g.42524947C>T |
| CLNSRC | OMIM Allelic Variant PharmGKB Clinical Annotation |
| CLNACC | RCV000018385.23, RCV000211167.1, RCV000211174.1, RCV000211232.1, RCV000211292.1, RCV000211293.1, RCV000211307.1, RCV000211390.1, RCV000211415.1, RCV000211422.1, RCV000342450.1, |
[PMID 28343093] Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.
