title: Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management.
abstract: Interindividual variability in analgesic effects of nonsteroidal anti-inflammatory drugs prescribed for sickle cell disease (SCD) pain is attributed to polymorphisms in the CYP2C8 and CYP2C9 enzymes. We described CYP2C8 and CYP2C9 genotype/phenotype profiles and frequency of emergency department (ED) visits for pain management in an African American SCD patient cohort. DNA from 165 unrelated patients was genotyped for seven CYP2C8 and 15 CYP2C9 alleles using the iPLEX ADME PGx multiplexed panel. CYP2C8*1 (0.806),*2 (0.164), *3 (0.018), and *4 (0.012) alleles were identified. Genotype frequencies were distributed as homozygous wild type (66.7%), heterozygous (27.8%), and homozygous variant/compound heterozygous (5.4%), respectively. CYP2C9*1 (0.824), *2 (0.027), *3 (0.012), *5 (0.009), *6 (0.009), *8 (0.042), *9 (0.061), and *11(0.015) were observed with extensive (68.5%), intermediate (18.1%) and poor predicted metabolizers (0.6%), respectively. Fifty-two and 55 subjects, respectively had at least one variant CYP2C8 or CYP2C9 allele. Although the distribution of the CYP2C9 (p = 0.0515) phenotypes was marginally significantly in high and low ED users; some CYP2C8 and CYP2C9 allelic combinations observed in 15.2% (25) of the cohort are associated with higher risks for analgesic failure. CYP2C8 and CYP2C9 preemptive genotyping could potentially enable clinicians to identify patients with impaired metabolic phenotypes.
authors: College of Nursing, University of Cincinnati, Cincinnati, Ohio, USA.
authors: Cheedy
authors: C
authors: Jaja
authors: Department of Medicine, Georgia Regents University, Augusta, Georgia, USA.
authors: Latanya
authors: L
authors: Bowman
authors: Department of Medicine, Georgia Regents University, Augusta, Georgia, USA.
authors: Leigh
authors: L
authors: Wells
authors: Department of Medicine, Georgia Regents University, Augusta, Georgia, USA.
authors: Niren
authors: N
authors: Patel
authors: Department of Biostatistics, Georgia Regents University, Augusta, Georgia, USA.
authors: Hongyan
authors: H
authors: Xu
authors: Department of Emergency Medicine Georgia Regents University, Augusta, Georgia, USA.
authors: Matt
authors: M
authors: Lyon
authors: Department of Medicine, Georgia Regents University, Augusta, Georgia, USA.
authors: Abdullah
authors: A
authors: Kutlar
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065729:Cytochrome P-450 CYP2C9; D065727:Cytochrome P-450 CYP2C8
keywords: CYP2C8; CYP2C9; NSAIDs; pharmacogenetics; sickle cell disease
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