The interesting thing about the CYP2D6 allele is that it's highly multigenic. There are many identified gene variants with gene deletions, duplications, and paired inheritance being possible. Pharmacogenomics, like any science, is evolving, and sometimes there is some inherent ambiguity to the results.
Using myself as an example. When I got my results back, the lab listed SIX probable results for my CYP2D6 phenotype. One of my alleles was definitive and coded for "no function"; the other was one of two structurally similar alleles, both coding for "normal function". The lab also determined that one of my alleles was duplicated, but which of two was uncertain. A duplicate "no function" allele doesn't create a "less than 0" functioning allele; 0+0 is still 0. However, a duplicate "normal function" allele DOES create a "greater than 1" functioning allele. Functional phenotype is determined by adding the scores of each allele. "Ultrarapid Metabolizer" is a score of >2.25, "Normal Metabolizer" is a "1.25-2.25", "Intermediate Metabolizer" is a 0.25-1, and "Poor Metabolizer" is a 0.
With my alleles being classified a "1 or 2" and a "0", I am potentially a "Normal Metabolizer" OR an "Intermediate Metabolizer". This DOES make a difference in whether certain drugs will/will not work for me. This is where a clinician needs to weigh all available information and make an educated recommendation. Because I have already had several poor responses to medications, I am fairly confident that the "no function" allele is the duplication and that my true phenotype is "Intermediate Metabolizer".
While I don't like uncertainty, coming across it in my OWN test results has given me some excellent questions to research ahead of seeing my first patients.
#Pharmacogenomics #CompleteMedicationManagement #PatientCare
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6dGreat insights! Consistency in gene expression is such a critical factor for improving efficiency in protein production. This highlights practical strategies to address bottlenecks and enhance reliability—essential for streamlining cell line development. Thanks Syngene International Limited for sharing!