Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management. Issue 4 (2nd February 2015)

• Record Type: Journal Article
• Authors: Jaja, Cheedy; Bowman, Latanya; Wells, Leigh; Patel, Niren; Xu, Hongyan; Lyon, Matt; Kutlar, Abdullah
• Is Part Of: Clinical and translational science. Volume 8:Issue 4(2015)
• Page Start: 272
• Page End: 280
• Publication Date: 2015-02-02
• Subjects: Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; 616.027
• DOI: 10.1111/cts.12260
• Languages: English
• ISSNs: 1752-8054

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Interindividual variability in analgesic effects of nonsteroidal anti‐inflammatory drugs prescribed for sickle cell disease (SCD) pain is attributed to polymorphisms in the <italic>CYP2C8</italic> and <italic>CYP2C9</italic> enzymes. We described <italic>CYP2C8</italic> and <italic>CYP2C9</italic> 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 <italic>CYP2C8</italic> and 15 <italic>CYP2C9</italic> alleles using the iPLEX ADME PGx multiplexed panel. <italic>CYP2C8*1</italic> (0.806), *<italic>2</italic> (0.164), *<italic>3</italic> (0.018), and *<italic>4</italic> (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. <italic>CYP2C9*1</italic> (0.824), <italic>*2</italic> (0.027), <italic>*3</italic> (0.012), <italic>*5</italic> (0.009), <italic>*6</italic> (0.009), <italic>*8</italic> (0.042), *<italic>9</italic> (0.061), and <italic>*11</italic>(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 <italic>CYP2C8</italic> or <italic>CYP2C9</italic> allele. Although the distribution of the <italic>CYP2C9</italic> (<italic>p</italic> = 0.0515) phenotypes was marginally significantly in high and low ED users; some <italic>CYP2C8</italic> and <italic>CYP2C9</italic> allelic combinations observed in 15.2% (25) of the cohort are associated with higher risks for analgesic failure. <italic>CYP2C8</italic> and <italic>CYP2C9</italic> preemptive genotyping could potentially enable clinicians to identify patients with impaired metabolic phenotypes.</p> </abstract>