title: Evaluation of a microarray-based genotyping assay for the rapid detection of cytochrome P450 2C19 *2 and *3 polymorphisms from whole blood using nanoparticle probes.
abstract: Numerous drugs such as clopidogrel have been developed to reduce coagulation or inhibit platelet function. The hepatic cytochrome P450 (CYP) pathway is involved in the conversion of clopidogrel to its active metabolite. A recent black-box warning was included in the clopidogrel package insert indicating a significant clinical link between specific CYP2C19 genetic variants and poor metabolism of clopidogrel. Of these variants, *2 and *3 are the most common and are associated with complete loss of enzyme activity. In patients who are carriers of a CYP2C19 *2 or *3 allele, the conversion of clopidogrel to its active metabolite may be reduced, which can lead to ischemic events and negative consequence for the patient. We examined the ability of the Verigene CLO assay (Nanosphere, Northbrook, IL) to identify CYP2C19 *2 and *3 polymorphisms in 1,286 unique whole blood samples. The Verigene CLO assay accurately identified homozygous and heterozygous *2 and *3 phenotypes with a specificity of 100% and a final call rate of 99.7%. The assay is fully automated and can produce a result in approximately 3.5 hours.
authors.affiliation: Dept. of Pathology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA.
authors.forename: Blake W
authors.initials: BW
authors.lastname: Buchan
authors.forename: Jess F
authors.initials: JF
authors.lastname: Peterson
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Cogbill
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Anderson
authors.forename: Joellen S
authors.initials: JS
authors.lastname: Ledford
authors.forename: Mary N
authors.initials: MN
authors.lastname: White
authors.forename: Neil B
authors.initials: NB
authors.lastname: Quigley
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Jannetto
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Ledeboer
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005838:Genotype; D006403:Hematologic Tests / Q000379:methods*; D006801:Humans; D054118:Nanospheres; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000378:metabolism; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine