Abstract
Objectives
To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population.
Methods
The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) protocol. The PCR products were digested with AvaII, KpnI or NsiI restriction enzymes. The digested products were separated using 8% polyacrylamide gel and stained by ethidium bromide. Genotyping of the subjects was done based on DNA fragment size.
Results
The frequencies of CYP2C9*1, *2 and *3 alleles in the Tamilian population were 0.907, 0.026 and 0.067, respectively. The distribution of CYP2C9*1/*1, *1/*2, *1/*3 and *2/*3 genotypes were 0.823, 0.044, 0.126 and 0.007, respectively.
Conclusion
CYP2C9*3 is the most frequent mutant allele found in the Tamilian population. The distribution of this mutant allele in the Tamilian population was found to be lesser than in Caucasians but higher than in Chinese.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Raucy JL, Allen SW (2001) Recent advances in P450 research. Pharmacogenomics J 1:178–186
Miners JO, Birkett DJ (1998) Cytochrome P450 2C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 45:525–538
Rogers JF, Nafziger AN, Bertino JS Jr (2002) Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450-metabolized drugs. Am J Med 113:746–750
Daly AK, King BP (2003) Pharmacogenetics of oral anticoagulants. Pharmacogenetics 13:247–252
Ingelman-Sundberg M, Daly AK, Newbert DW (2003) Homepage of the human cytochrome P450 (CYP) allele nomenclature committee. URL:http://www.imm.ki.se/cypalleles/ cyp2c9.htm. (ref type: electronic citation, accessed on 10/07/2003)
Lee CR, Goldstein JA, Pieper JA (2002) Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in- vitro and human data. Pharmacogenetics 12:251–263
Aithal GP, Day CP, Kesteven PJ, Daly AK (1999) Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 353:717–719
Rettie AE, Wienkers LC, Gonzalez FJ, Trager WF, Korzekwa KR (1994) Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics 4:39–42
Miners J (2002) CYP2C9 polymorphism: impact on tolbutamide pharmacokinetics and response. Pharmacogenetics 12:91–92
van der WJ, Steijns LS, van Weelden MJ, de Haan K (2001) The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics 11:287–291
Verstuyft C, Morin S, Robert A, Loriot MA, Beaune P, Jaillon P, Becquemont L (2001) Early acenocoumarol overanticoagulation among cytochrome P450 2C9 poor metabolizers. Pharmacogenetics 11:735–737
Gaedigk A, Casley WL, Tyndale RF, Sellers EM, Jurima-Romet M, Leeder JS (2001) Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations. Can J Physiol Pharmacol 79:841–847
Wang SL, Huang J, Lai MD, Tsai JJ (1995) Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. Pharmacogenetics 5:37–42
Krishnamurthi B (2003) The Dravidian languages. Cambridge University Press, Cambridge
Desai A (2001) The Original Indians: an enquiry. Media house, New Delhi
Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, Miners JO, Birkett DJ, Goldstein JA (1996) The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 6:341–349
Crespi CL, Miller VP (1997) The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. Pharmacogenetics 7:203–210
Scordo MG, Pengo V, Spina E, Dahl ML, Gusella M, Padrini R (2002) Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin Pharmacol Ther 72:702–710
Kidd RS, Straughn AB, Meyer MC, Blaisdell J, Goldstein JA, Dalton JT (1999) Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics 9:71–80
Ninomiya H, Mamiya K, Matsuo S, Ieiri I, Higuchi S, Tashiro N (2000) Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Ther Drug Monit 22:230–232
Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J (2002) Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics 12:571–580
Kirchheiner J, Meineke I, Freytag G, Meisel C, Roots I, Brockmoller J (2002) Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther 72:62–75
Kirchheiner J, Brockmoller J, Meineke I, Bauer S, Rohde W, Meisel C, Roots I (2002) Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin Pharmacol Ther 71:286–296
Aithal GP, Day CP, Leathart JB, Daly AK (2000) Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis. Pharmacogenetics 10:511–518
Acknowledgments
This research project was funded by the Indian Council of Medical Research, New Delhi, India, and INSERM, Paris, France (ICMR ref. no.50/6/2000-BMS, dated 11/12/2001). Technical assistance provided by Mr. Rajan is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Adithan, C., Gerard, N., Vasu, S. et al. Allele and genotype frequency of CYP2C9 in Tamilnadu population. Eur J Clin Pharmacol 59, 707–709 (2003). https://doi.org/10.1007/s00228-003-0666-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-003-0666-3