Pharmacogenomic Biomarkers of Susceptibility to Adverse Drug Reactions: Just Around the Corner or Pie in the Sky?

Mark I. Avigan


Personalized Medicine. 2009;6(1):67-78. 

In This Article

Inheritance Characteristics of Genetically Determined ADR Susceptibility

In developing a vision for future discovery of new pharmacogenomic biomarkers that will improve drug risk management, it should be noted that there are two general types of inheritance for genetic susceptibility to ADRs. As discussed below, the way in which the phenotypic trait can be genetically transmitted will have a strong impact on the predictive value for ADR susceptibility of the individual biomarker.

The first category of hereditary transmission of disease or ADR susceptibility is the classical Mendelian form. In this case, a single allelic locus carries the trait that is transmitted either in a dominant or recessive fashion. For a well-defined ADR phenotype, correlation with a specific gene locus is relatively straight forward. It is no surprise that one of the earliest discovered pharmacogenomic markers for ADR susceptibility was the X-linked locus linked to G6PD deficiency.[104] Specific genetic mutations in the G6PD gene in males have strong predictive value for transmission of susceptibility to hemolysis induced by certain drugs.[18,19,104] The other category of hereditary transmission of disease or ADR susceptibility is more complex and reflects potential combinatorial effects of genomic variations at multiple genetic loci, as well as nongenetic risk factors.[20,21] It appears that a number of genetically transmitted disease or drug-related ADR susceptibility markers fall into this category.[21]