Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management

Cheedy Jaja, Latanya Bowman, Leigh Wells, Niren Patel, Hongyan Xu, Matthew L Lyon, Abdullah Kutlar

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)272-280
Number of pages9
JournalClinical and Translational Science
Volume8
Issue number4
DOIs
StatePublished - Aug 1 2015

Fingerprint

Sickle Cell Anemia
Non-Steroidal Anti-Inflammatory Agents
Pain Management
Disease Management
Metabolism
Alleles
Phenotype
Analgesics
Hospital Emergency Service
Genotype
Cytochrome P-450 CYP2C8
Cytochrome P-450 CYP2C9
Polymorphism
African Americans
Anti-Inflammatory Agents
Pain
DNA
Enzymes
Pharmaceutical Preparations

Keywords

  • CYP2C8
  • CYP2C9
  • NSAIDs
  • Pharmacogenetics
  • Sickle cell disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management. / Jaja, Cheedy; Bowman, Latanya; Wells, Leigh; Patel, Niren; Xu, Hongyan; Lyon, Matthew L; Kutlar, Abdullah.

In: Clinical and Translational Science, Vol. 8, No. 4, 01.08.2015, p. 272-280.

Research output: Contribution to journalArticle

@article{ea648acd75674797a24e8ec00ef6b849,
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.",
keywords = "CYP2C8, CYP2C9, NSAIDs, Pharmacogenetics, Sickle cell disease",
author = "Cheedy Jaja and Latanya Bowman and Leigh Wells and Niren Patel and Hongyan Xu and Lyon, {Matthew L} and Abdullah Kutlar",
year = "2015",
month = "8",
day = "1",
doi = "10.1111/cts.12260",
language = "English (US)",
volume = "8",
pages = "272--280",
journal = "Clinical and Translational Science",
issn = "1752-8054",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management

AU - Jaja, Cheedy

AU - Bowman, Latanya

AU - Wells, Leigh

AU - Patel, Niren

AU - Xu, Hongyan

AU - Lyon, Matthew L

AU - Kutlar, Abdullah

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

KW - CYP2C8

KW - CYP2C9

KW - NSAIDs

KW - Pharmacogenetics

KW - Sickle cell disease

UR - http://www.scopus.com/inward/record.url?scp=84940030745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940030745&partnerID=8YFLogxK

U2 - 10.1111/cts.12260

DO - 10.1111/cts.12260

M3 - Article

C2 - 25640739

AN - SCOPUS:84940030745

VL - 8

SP - 272

EP - 280

JO - Clinical and Translational Science

JF - Clinical and Translational Science

SN - 1752-8054

IS - 4

ER -