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rs1065852

From SNPedia

CYP2D6 drug metabolism
Orientationminus
Stabilizedminus
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.
ReferenceGRCh37 37.1/131
Chromosome22
Position42526694
GeneCYP2D6
is asnp
is mentioned by
dbSNPrs1065852
ebirs1065852
HLIrs1065852
Exacrs1065852
Varsomers1065852
Maprs1065852
PheGenIrs1065852
hapmaprs1065852
1000 genomesrs1065852
hgdprs1065852
ensemblrs1065852
gopubmedrs1065852
geneviewrs1065852
scholarrs1065852
googlers1065852
pharmgkbrs1065852
gwascentralrs1065852
openSNPrs1065852
23andMers1065852
23andMe allrs1065852
SNP Nexus

SNPshotrs1065852
SNPdbers1065852
MSV3drs1065852
GWAS Ctlgrs1065852
GMAF0.2557
Max Magnitude3.2

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 [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.

It is also suggested that poor metabolizers of debrisoquine will be poor metabolizers of metoprolol, diltiazem (brand name cardizem), and propafenone. [PMID 3437726]

OMIM124030
DescDEBRISOQUINE, POOR METABOLISM OF
Variant0005
Relatedalso




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
CLNACC RCV000018389.23,



[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.

[PMID 18698231OA-icon.png] Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.

[PMID 20174590OA-icon.png] 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.


GET Evidence
CYP2D6-P34S
aa_change Pro34Ser
aa_change_short P34S
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.187302
summary This variant is associated with poor metabolism of debrisoquine. The variant is also known as CYP2D6*10 or CYP2D6 (J) or CYP2D6 (Ch1, Ch2). Zateyshchikov et al. report that heterozygotes carrying this variant are more sensitive to betaxolol therapy.



[PMID 24302953OA-icon.png] CYP2D6 P34S Polymorphism and Outcomes of Escitalopram Treatment in Koreans with Major Depression


[PMID 23133420OA-icon.png] 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 24528284OA-icon.png]
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