9.5 Limitations of Pharmacogenomic Testing

Star Allele System

Many key genes in pharmacogenomics use a ‘star allele’ system, where a single star allele (e.g. *3) defines a certain combination of one or more genetic variants found together in that allele. You can find many of these definitions on the PharmVar website. Genes can have many star alleles; the enzyme CYP2C9, for example, has over 60 known star alleles.’

Pharmacogenomic tests tend to only test for some of the most common star alleles, meaning that rare alleles will not be detected. Additionally, different tests may test for different alleles. For example, one test may test for the presence of the *2, *3, *5, *8 or *11 alleles of CYP2C9, while another may only test for *2 or *3.

If a person has a star allele not detected by the pharmacogenomic test, they default to the *1 allele, which is the ‘reference’ or ‘normal’ version of the gene. However, this does not mean that the person definitely has the *1 allele, and there is a significant possibility that they may carry a star allele, which could affect drug response, but the pharmacogenomic test does not detect that.

Some pharmacogenomic tests may test for the presence of a certain star allele by only looking for one particular change found in that star allele rather than all the changes which define the star allele. As some changes can be found in several different star alleles of the same gene, this can confuse which allele is actually present.

Finally, as pharmacogenomics research continues, new star alleles are found, while other star alleles may have their function assignment changed (e.g. an ‘uncertain function’ star allele may be changed to ‘decreased function’ based on new evidence). PharmVar is regularly updated with new star alleles and their functions as information becomes available.

Attribution & References

Except where otherwise noted, this page is adapted from What are the limitations of pharmacogenomic testing? by PharmGKB, CC BY-SA 4.0