Abstract
Objective
To determine the frequencies of two functional single nucleotide polymorphisms, CYP3A5*3 and CYP3A5*6, in the CYP3A5 gene in three distinct Asian ethnic groups, namely, the Chinese, Malays and Indians.
Methods
Single nucleotide polymorphism analyses of CYP3A5*1, *3 and *6 were performed in 296 healthy subjects (108 Chinese, 98 Malays and 90 Indians) using the polymerase chain reaction-restriction fragment length polymorphism method.
Results
The *1 allele frequency was 25% in Chinese compared with 40% in Malays and Indians (P=0.001). The *3 allele frequency was also higher in the Chinese population, being 76% versus 60% in the Malays and Indians (P=0.001). The Malays and Indians also had allele frequencies significantly different from Caucasian, Japanese and African-American populations (each P≤0.001) previously published in the literature. The *6 allele was not detected in any the three Asian ethnic groups analysed.
Conclusion
These results seem to suggest that genetic polymorphisms in CYP3A5 in Asians, in particular Malays and Indians but also Chinese although to a lesser extent, may be an important genetic contributor to interindividual as well as interethnic differences in clearance of CYP3A substrates.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Nelson DR (1999) Cytochrome P450 and the individuality of species. Arch Biochem Biophys 369:1–10
Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC, Nebert DW (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers, and nomenclature. Pharmacogenetics 6:1–41
Shimada T, Yamazaki H, Mumura M, Inui Y, Guengerich FP (1994) Interindividual variations in human liver cytochrome P450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414–423
Wrighton SA, Ring BJ, Watkins PB, VandenBranden M (1989) Identification of a polymorphically expressed member of the human cytochrome P-450III family. Mol Pharmacol 36:97–105
Domanski TL, Finta C, Halpert JR, Zaphiropoulos PG (2001) cDNA cloning and initial characterisation of CYP3A43, a novel human cytochrome P450. Mol Pharmacol 59:386–392
Hirth J, Watkins PB, Strawderman M, Schott A, Bruno R, Baker LH (2000) The effect of an individual's cytochrome CYP3A4 activity on docetaxel clearance. Clin Cancer Res 6:1255–1258
Schuetz J, Beach P, Guzelian PS (1994) Selective expression of cytochrome P450 CYP3A mRNAs in embyonic and adult human liver. Pharmacogenetics 5:11–20
Eiselt R, Domanski TL, Zibat A, Mueller R, Presecan-Siedel E, Hustert E, Zanger UM, Brockmoller J, Klenk HP, Meyer UA, Khan KK, He YA, Halpert JR, Wojnowski L (2001) Identification and functional characterisation of eight CYP3A4 protein variants. Pharmacogenetics 11:447–458
Hustert E, Huberl M, Burk O, Wolbold R, He YQ, Klein K, Nuessler AC, Neuhaus P, Klattig J, Eiselt R, Koch I, Zibat A, Brockmoller J, Halpert JR, Zanger UM, Wojnowki L (2001) The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 11:773–779
Chowbay B, Cumaraswamy S, Cheung YB, Zhou Q, Lee EJ (2003) Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients. Pharmacogenetics 13:89–95
Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Venkataramanan R, Strom S, Thummel K, Boguski MS, Schuetz E (2001) Sequence diversity in CYP3A4 promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 27:383–391
Fukuen S, Fukuda T, Maune H, Ikenaga Y, Yamamoto I, Inaba T, Azuma J (2002) Novel detection assay by PCR-RFLP and frequency of the CYP3A5*3 and *6, in a Japanese population. Pharmacogenetics 12:331–334
Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA (2002) Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos 30:883–891
Anttila S, Hukkanen J, Hakkola J, Stjernvall T, Beaune P, Edwards RJ, Boobis AR, Pelkonen O, Raunio H (1997) Expression and localization of CYP3A4 and CYP3A5 in human lung. Am J Respir Cell Mol Biol 16:242–249
Acknowledgement
We acknowledge Caroline Kibat for her excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Balram, C., Zhou, Q., Cheung, Y.B. et al. CYP3A5*3 and *6 single nucleotide polymorphisms in three distinct Asian populations. Eur J Clin Pharmacol 59, 123–126 (2003). https://doi.org/10.1007/s00228-003-0594-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-003-0594-2