title: Progressing Preemptive Genotyping of CYP2C19 Allelic Variants for Sickle Cell Disease Patients.
abstract: OBJECTIVE
  Interindividual variability in drug response and adverse effects have been described for proton pump inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, tricyclic antidepressants, and anti-infectives, but little is known about the safety and efficacy of these medications in patients with sickle cell disease (SCD). We genotyped the CYP2C19 gene which has been implicated in the metabolism of these drugs in an SCD patient cohort to determine the frequencies of reduced function, increased function, or complete loss-of-function variants.
  
  
  METHODS
  DNAs from 165 unrelated SCD patients were genotyped for nine CYP2C19 (*2, *3, *4, *5, *6, *7,*8, *12, and *17) alleles using the iPLEX®ADME PGx multiplex panel.
  
  
  RESULTS
  Three CYP2C19 alleles (*2, *12, and *17) were detected with the following frequencies: 0.209, 0.006, and 0.236, respectively. The predicted phenotype frequencies were distributed as extensive (31.5%), intermediate (24.8%), poor (5.5%), ultrarapid (30.3%), and unknown metabolizers (7.9%).
  
  
  CONCLUSIONS
  Prognostic genotyping is potentially useful for identifying SCD patients with allelic variants linked to proven clinical pharmacokinetic consequences for several drugs metabolized by the CYP2C19 gene. However, the main challenge to implementing a genetics-guided prescribing practice is ensuring concordance between CYP2C19 genotypes and metabolic phenotypes in SCD patients.
authors.affiliation: 1 College of Nursing, University of Cincinnati , Cincinnati, Ohio.
authors.forename: Cheedy
authors.initials: C
authors.lastname: Jaja
authors.affiliation: 2 Department of Medicine, Georgia Regents University , Augusta, Georgia .
authors.forename: Nadine
authors.initials: N
authors.lastname: Barrett
authors.affiliation: 2 Department of Medicine, Georgia Regents University , Augusta, Georgia .
authors.forename: Niren
authors.initials: N
authors.lastname: Patel
authors.affiliation: 3 Department of Emergency Medicine, Georgia Regents University , Augusta, Georgia .
authors.forename: Matt
authors.initials: M
authors.lastname: Lyon
authors.affiliation: 4 Department of Biostatistics, Georgia Regents University , Augusta, Georgia .
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: 2 Department of Medicine, Georgia Regents University , Augusta, Georgia .
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kutlar
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants
chemical_list: C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
keywords: drug metabolizing enzyme; pharmacogenetics; precision medicine; preemptive genotyping; sickle cell disease