Rs1065852

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 is observed.

Other drugs metabolized by CYP2D6 include dextromorphan, sparteine, nortriptyline, atomoxetine, and codeine.

Nakamura et al 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.

Genotyping panel for assessing response to cancer chemotherapy.

Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.

Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms.

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.