Journal of Postgraduate Medicine
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Year : 2006  |  Volume : 52  |  Issue : 4  |  Page : 245  

CYP2D6 genotype and phenotype relationship in South Indians

I Rusli 
 Department of Pharmacology, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia

Correspondence Address:
I Rusli
Department of Pharmacology, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan
Malaysia




How to cite this article:
Rusli I. CYP2D6 genotype and phenotype relationship in South Indians.J Postgrad Med 2006;52:245-245


How to cite this URL:
Rusli I. CYP2D6 genotype and phenotype relationship in South Indians. J Postgrad Med [serial online] 2006 [cited 2020 Apr 7 ];52:245-245
Available from: http://www.jpgmonline.com/text.asp?2006/52/4/245/28141


Full Text

The Indian population is interesting in relation to CYP2D6 polymorphisms, India being mid-way between the east and the west, two populations with clear geographic demarcations in terms of the polymorphisms. The ancestors of Indians may have come from regions in Europe unlike the ancestors of most other Asian ethnic groups.[1],[2],[3],[4] Indeed our own study[5] showed that Malaysians of Indian descent show characteristics that are intermediate between the east and the west, showing types and frequencies of CYP2D6 alleles that are significantly different from what was expected of an Asian population. With many drugs that are substrates of CYP2D6 , the clinical significance may be important. There is however a dearth of data from India and the study describes a phenotyping study in Indian subjects.[6] Purportedly it was to determine if Indian subjects showed discrepant genotype-phenotype relationship, the reason for which was not very clearly stated. Generally the genotype-phenotype relationship is good except where the populations carry novel alleles that are not detected by the allele-specific methods used in the particular study. Nevertheless this Indian study was probably overambitious. To test phenotype-genotype associations, a larger number of subjects is needed. Due to cost constraints, however, that is usually not possible. Notwithstanding that, sample sizes should have been calculated using appropriate power formulas and measures of central tendencies and variances of index parameters (e.g., metabolic ratios) and the fact alluded to in the discussions for considerations of potential pitfalls in conclusions. This is important because, whereas, arguably, genotyping is more specific, phenotyping is subject to many potential confounders. Phenotyping indicators like metabolic ratios are expected to be within a range for each genotype group and comparisons are made using appropriate statistics. The challenge would be to discern if differences observed are true differences or whether they arise from uncertainties related to confounders and assay errors. With small sample sizes this would be even more challenging. The authors could probably have confined themselves to studying smaller genotype groups of relevance to their population with sufficient numbers of subjects in each group. The more commonly found genotype groups should probably be chosen to infer on clinical relevance. They could potentially take advantage of the peculiarity of their population in terms of the frequencies for CYP2D6*4 and CYP2D6*10 and thus study groups CYP2D6*4/*4, CYP2D6*4/*10 and CYP2D6*10/*10. Such groups may not be easily found in other populations in the east or the west.

References

1Abraham BK, Adithan C, Shashindran CH, Vasu S, Alekutty NA. Genetic polymorphism of CYP2D6 in a Keralite (South India) population. Br J Clin Pharmacol 2000;49:285-6.
2Lamba V, Lamba JK, Dilawari JB, Kohli KK. Genetic polymorphism of CYP2D6 in North Indian subjects. Eur J Clin Pharmacol 1998;54:787-91.
3Masimirembwa C, Persson I, Bertilsson L, Hasler J, Ingelman-Sundberg M. A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: Association with diminished debrisoquine hydroxylase activity. Br J Clin Pharmacol 1996;42:713-9.
4Gan SH, Ismail R, Wan Adnan WA, Wan Z. Correlation of tramadol pharmacokinetics and CYP2D610 genotype in Malaysian subjects. J Pharm Biomed Anal 2002;30:189-95.
5Ismail R, Teh LK. Genetic polymorphism of CYP2D6: Malaysian Indians have the highest frequency for CYP2D64 in Asia. Eur J Clin Pharmacol 2001;57: 617-8.
6Naveen AT, Prasanna T, Farzana BL, Rajan S, Adithan C. CYP2D6 genotype and phenotype relationship in South Indians. J Postgrad Med 2006;52:253-6.

 
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