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 [PMID 2211621] is observed.

Other drugs metabolized by CYP2D6 include dextromorphan, sparteine, nortriptyline, 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 Orientals show lower metabolic activities than Caucasians for drugs metabolized mainly by CYP2D6, since this (T) allele occurs in higher frequency in Orientals.

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