rs1065852
| CYP2D6 drug metabolism |
| Orientation | minus |
| Stabilized | minus |
| Geno | Mag | Summary |
|---|---|---|
| (C;C) | 0 | normal |
| (C;T) | 2 | Carrier of one CYP2D6 decreased or non-functioning variant. |
| (T;T) | 3.2 | Homozygous for CYP2D6 decreased or non-functioning variants; possibly less response to some drugs, including tamoxifen |
| Reference | GRCh37 37.1/131 |
| Chromosome | 22 |
| Position | 42130692 |
| Gene | CYP2D6, LOC102723722, LOC107987465, LOC107987481 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs1065852 |
| dbSNP (classic) | rs1065852 |
| ClinGen | rs1065852 |
| ebi | rs1065852 |
| HLI | rs1065852 |
| Exac | rs1065852 |
| Gnomad | rs1065852 |
| Varsome | rs1065852 |
| LitVar | rs1065852 |
| Map | rs1065852 |
| PheGenI | rs1065852 |
| Biobank | rs1065852 |
| 1000 genomes | rs1065852 |
| hgdp | rs1065852 |
| ensembl | rs1065852 |
| geneview | rs1065852 |
| scholar | rs1065852 |
| rs1065852 | |
| pharmgkb | rs1065852 |
| gwascentral | rs1065852 |
| openSNP | rs1065852 |
| 23andMe | rs1065852 |
| SNPshot | rs1065852 |
| SNPdbe | rs1065852 |
| MSV3d | rs1065852 |
| GWAS Ctlg | rs1065852 |
| GMAF | 0.2557 |
| Max Magnitude | 3.2 |
Also known as c.100C>T (p.Pro34Ser or P34S), the wild type (normal) allele at this SNP is (C). The (T) variant indicates the presence of a non-wild type CYP2D6 variant, but it appears in many different variants so it can not be used to determine the presence of any particular variant. The most common variants it appears in are CYP2D6*10 and CYP2D6*4, but these are not the only ones. While this is the defining mutation for CYP2D6*10, it is not possible by itself for this mutation to determine a particular variant. In addition, the CYP2D6*4 variant includes this mutation, but the defining mutation 1846G>A SNP is not available in the common direct to consumer testing services.
While it is not possible for this mutation to identify one particular variant, all the variants in which it appears have reduced or no CYP2D6 activity.
If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine [PMID 2211621] is observed.
Other drugs metabolized by CYP2D6 include dextromorphan, sparteine, nortriptyline, atomoxetine [16041391?dopt=Abstract PMID 16041391], and codeine.
Nakamura et al [PMID 12051754] suggest that thermal instabilities and reduced intrinsic clearance by the protein encoded by the rs1065852(T) allele are the main reasons Asians show lower metabolic activities than Caucasians for drugs metabolized mainly by CYP2D6, since this (T) allele occurs in higher frequency in Asians.
A study of several hundred Chinese breast cancer patients treated with either tamoxifen or toremifene reported that for the 50 women who were CYP2D6*10 homozygotes (i.e. rs1065852(T;T)), the group treated with toremifene had a significantly higher 5-year disease-free survival (DFS) rate than the group treated with tamoxifen (90.9% vs. 67.9%, p = 0.031). For the remaining rs1065852 (C;C) and (C;T) patients, there was no significant difference between the 5-year DFS rates of those treated with one drug versus the other.[PMID 29978573]
It is also suggested that poor metabolizers of debrisoquine will be poor metabolizers of metoprolol, diltiazem (brand name cardizem), and propafenone. [PMID 3437726]
| ClinVar | |
|---|---|
| Risk | Rs1065852(T;T) |
| Alt | Rs1065852(T;T) |
| Reference | Rs1065852(C;C) |
| Significance | Drug-response |
| Disease | Debrisoquine |
| Variation | info |
| Gene | CYP2D6 |
| CLNDBN | Debrisoquine, poor metabolism of |
| Reversed | 1 |
| HGVS | NC_000022.10:g.42526694G>A |
| CLNSRC | OMIM Allelic Variant UniProtKB (protein) |
| CLNACC | RCV000018389.23, |
[PMID 18547414
] Genotyping panel for assessing response to cancer chemotherapy.
[PMID 18698231] Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.
[PMID 20174590] Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms.
[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 24302953] CYP2D6 P34S Polymorphism and Outcomes of Escitalopram Treatment in Koreans with Major Depression
[PMID 23133420] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
[PMID 25159483] Cytochrome P450 2D6*10 genotype affects the pharmacokinetics of dimemorfan in healthy Chinese subjects
| GWAS snp | |
|---|---|
| PMID | [PMID 24528284]
|
| Trait | Response to serotonin reuptake inhibitors in major depressive disorder (plasma drug and metabolite levels) |
| Title | Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations. |
| Risk Allele | |
| P-val | 2E-16 |
| Odds Ratio | NR NR |
[PMID 28343093] Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.
