CYP2C9 allelic variants and frequencies in a pediatric sickle cell disease cohort: Implications for NSAIDs pharmacotherapy

Cheedy Jaja, Niren Patel, Stuart A. Scott, Robert W Gibson, Abdullah Kutlar

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain in patients with sickle cell disease (SCD) are metabolized by the CYP2C9 enzyme. Racial differences in CYP2C9 allele frequencies impact NSAIDs efficacy and safety. We determined the frequencies of CYP2C9 alleles in an African American pediatric SCD cohort. Genomic DNA was isolated from blood samples of 30 patients aged between 7 and 17 years. Genotyping of nine CYP2C9 alleles (*1,*2, *3, *4, *5, *6, *8, *11, and *13) was performed using restriction fragment length polymorphism-PCR assays and the Tag-It™ Mutation Detection System. The wild type *1 allele frequency was 0.850. The most common variant allele detected was CYP2C9*8 (0.067). The combined frequency of the *2, *5, *6, *8, and *11 variants was 0.151. Seventy percent of the study cohort were predicted extensive metabolizers (*1/*1) and 30% were intermediate metabolizers due mainly to the *1/*8 genotype. Analysis of CYP2C9 using an expanded assay panel facilitated improved classification of predicted drug metabolic phenotypes in our cohort. However, the pharmacokinetic effects of the CYP2C9*5,*6,*8, and *11 alleles on NSAIDs metabolism has not been evaluated and underscores the need for studies on substrate-specific effects of variant alleles common in populations with genetic susceptibility to SCD.

Original languageEnglish (US)
Pages (from-to)396-401
Number of pages6
JournalClinical and Translational Science
Volume7
Issue number5
DOIs
StatePublished - Oct 1 2014

Fingerprint

Drug therapy
Pediatrics
Sickle Cell Anemia
Anti-Inflammatory Agents
Drug Therapy
Pharmaceutical Preparations
Alleles
Gene Frequency
Assays
Pharmacokinetics
Population Genetics
Genetic Predisposition to Disease
Cytochrome P-450 CYP2C9
Polymorphism
Metabolism
Restriction Fragment Length Polymorphisms
African Americans
Blood
Cohort Studies
Genotype

Keywords

  • CYP2C9
  • Genotyping
  • NSAIDs
  • Pharmacogenetics
  • Sickle cell disease

ASJC Scopus subject areas

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

Cite this

CYP2C9 allelic variants and frequencies in a pediatric sickle cell disease cohort : Implications for NSAIDs pharmacotherapy. / Jaja, Cheedy; Patel, Niren; Scott, Stuart A.; Gibson, Robert W; Kutlar, Abdullah.

In: Clinical and Translational Science, Vol. 7, No. 5, 01.10.2014, p. 396-401.

Research output: Contribution to journalArticle

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