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Departments of
1
Clinical Chemistry and
2
Pediatrics, Sophia Children’s Hospital, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
3 Division of Pediatric Clinical Pharmacology, Children’s National Medical Center, Washington, DC 20010.
4 Departments of Pediatrics and Pharmacology, George Washington University Medical Center, Washington, DC 20037.
aAddress correspondence to this author at: Department of Clinical Chemistry, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Fax 31-10-436-7894; e-mail vanschaik{at}ckcl.azr.nl.
Background: Enzymes of the cytochrome P450 3A (CYP3A) family are responsible for the metabolism of >50% of currently prescribed drugs. CYP3A5 is expressed in a limited number of individuals. The absence of CYP3A5 expression in 
70% of Caucasians was recently correlated to a genetic polymorphism (CYP3A5*3). Because CYP3A5 may represent up to 50% of total CYP3A protein in individuals polymorphically expressing CYP3A5, it may have a major role in variation of CYP3A-mediated drug metabolism. Using sequencing, have been identified (Hustert et al. Pharmacogenetics 2001;11:773–9; Kuehl et al. Nat Genet 2001;27:383–91) variant alleles *2 through *7 for CYP3A5. Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in specific ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy.
Methods: In a group of 500 healthy Dutch Caucasian blood donors, we determined the allelic frequency of the CYP3A5*2, *3, *4, *5, *6, and *7 alleles by use of newly developed PCR-restriction fragment length polymorphism assays.
Results: The frequency of the defective CYP3A5*3 allele in the Dutch Caucasian population was 91%, followed by the CYP3A5*2 (1%) and CYP3A5*6 (0.1%) alleles. The CYP3A5*4, *5, and *7 alleles were not detected.
Conclusions: On the basis of its allelic frequency, screening for the CYP3A5*3 allele in the Caucasian population is extremely relevant. In addition, screening for the CYP3A5*2 allele may be taken into consideration in individuals heterozygous for the CYP3A5*3 allele. The CYP3A5*4, *5, *6, and *7 alleles have low allelic frequencies that do not support initial screening.
The following articles in journals at HighWire Press have cited this article:
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