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 language | English (US) |
|---|---|
| Pages (from-to) | 396-401 |
| Number of pages | 6 |
| Journal | Clinical and Translational Science |
| Volume | 7 |
| Issue number | 5 |
| DOIs | |
| State | Published - Oct 1 2014 |
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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 journal › Article
}
TY - JOUR
T1 - CYP2C9 allelic variants and frequencies in a pediatric sickle cell disease cohort
T2 - Implications for NSAIDs pharmacotherapy
AU - Jaja, Cheedy
AU - Patel, Niren
AU - Scott, Stuart A.
AU - Gibson, Robert W
AU - Kutlar, Abdullah
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
KW - CYP2C9
KW - Genotyping
KW - NSAIDs
KW - Pharmacogenetics
KW - Sickle cell disease
UR - http://www.scopus.com/inward/record.url?scp=84911808190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84911808190&partnerID=8YFLogxK
U2 - 10.1111/cts.12172
DO - 10.1111/cts.12172
M3 - Article
C2 - 24889181
AN - SCOPUS:84911808190
VL - 7
SP - 396
EP - 401
JO - Clinical and Translational Science
JF - Clinical and Translational Science
SN - 1752-8054
IS - 5
ER -