Table 1.
FDA approved/recommended screening assays.
| Screening Test | Polymorphisms Represented | Pertinent Pharmaceuticals Represented | Limitations |
|---|---|---|---|
| Roche CYP2D6/2C19 AmpliChip® | 33 CYP2D6 and 2 CYP19 distinct alleles | 25% of known pharmaceuticals[28]. | Only represents 25% of known CYP2D6 and only 5.5% of known CYP2C19 polymorphisms. |
| Affymetrix Drug Metabolizing Enzyme and Transporters (DMET) | 225 genes involved in drug absorption, distribution, metabolism, and elimination. | Virtually all pharmaceuticals may be affected by polymorphisms one of these enzymes. | It is unclear how to clinically interpret this matrix output. |
| HLA-B 5701 | HLA-B*5701 | Presence of this polymorphism is associated with 47% PPV and 99% NPV of Abacavir hypersensitivity[17] | Poor PPV (due to low prevalence of polymorphism) may inappropriately exclude therapy from some patients. |
| Genelex CYP2C9 and VKORC | CYP2C9*1, *2, *3 and VKORC1 -1639 | Warfarin dosing[18] | Screening explains only approx 40% of dosing variation[84]. |
| HLA-B*1502 | HLA-B*1502 | Carbamazepine associated Stevens-Johnson Syndrome or toxic epidermal necrolysis in Asian populations[85]. | Limited to patients of Asian decent. |
| HLA-A*3101 | HLA-A*3101 | Carbamazepine associated hypersensitivity reactions in European populations[78]. | NNT equals 39 European patients, 56 Japanese patients and 83 patients of un-determined decent. |
| HER2 (INFORMR HER2 FISH test, PathVysion® HER2 FISH test, PharmaDX® HER2 FISH test, Spot-Light® HER2 CISH test) | Number HER2 gene copies | Herceptin efficacy in breast[86] and gastric[86] cancer. | Equivocal results should be confirmed by a second screening method. 4 FDA approved genetic methods available. |
| CYP2C19 | CYP2C19 metabolizer status | Poor metabolizers do not form active metabolite of clopidogrel[25]. | Improved outcomes have been demonstrated in Chinese patients[30] only and no major society recommends genotyping prior to therapy to date. |
| G6PD | G6PD mutation by semi-quantitative or spectrophotometric methods[64] | High risk of hemolysis in patients receiving dapsone, methylene blue, nitrofurantoin, phenazopyridine, primaquine, rasburicase, and toluidine blue[87]. | Initial semi-quantitative analysis should be confirmed by spectrophotometric method due to wide variability of enzyme function. |
PPV: positive predictive value
NNT: number needed to treat