CYP26 Genetic Polymoprhism

CYP2D6 is a highly polymorphic gene. CYP2D6 alleles have been extensively studied in multiple geographically diverse, ancestry diverse, and ethnically diverse groups, and significant differences in allele frequencies have been observed.

The most commonly reported alleles are categorised into functional groups as follows: normal function (e.g., CYP2D61, 2, and 35), decreased function (e.g., CYP2D6 9, 10, 17, 29, and 41), and no function (e.g., CYP2D6 3–6).

Ultra Metabolisers (UM)

Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.

The prevalence of CYP2D6 UM varies but is thought to be present in approximately 1–10% of Caucasians (European, North American), 3–4% of Blacks (African Americans), and 1–2% of East Asians (Chinese, Japanese, Korean). The frequency of UM phenotype has been reported to be even higher in some groups, including Ashkenazi Jews and regional populations in the Middle East.

Normal Metabolisers (NM)

Between 43–67% of individuals have 2 normal-function alleles (1 or 2), or one normal-function allele and one decreased-function allele, resulting in a “normal metaboliser” phenotype based on the CPIC/PharmGKB activity scores. These individuals are most likely to have a phenotypically normal response to tramadol. However, there is a large amount of variability in tramadol response within individuals genotyped as normal metabolisers (NMs), and the causes of this variation, among individuals with the same diplotype, are unknown.

Intermediate Metabolisers (IM)

Between 10–44% of individuals are IMs—they have either 2 decreased-function alleles or one normal- or decreased-function and one no-function allele. PharmGKB reports that the highest frequency of IM activity scores are found in Sub-Saharan-African and East-Asian populations

Poor Metabolisers (PM)

Avoid codeine use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-tramadol opioid.

Related disorders

Currently, there are no diseases or conditions which have been consistently linked to variation in the CYP2D6 genes independent of drug metabolism or drug response.

Use of codeine or tramadol in tonsillectomy/adenoidectomy

Several regulatory agencies worldwide advise against the use of codeine and tramadol in children younger than 12 years of age, and in children younger than 18 years of age after tonsillectomy and/or adenoidectomy. There may be a role for genotype-guided use of codeine in specific paediatric patient populations.