Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 52, Num. 4, 2006, pp. 245-245

Journal of Postgraduate Medicine, Vol. 52, No. 4, October-December, 2006, pp. 245

Expert's Comments

CYP2D6 genotype and phenotype relationship in South Indians

Ismail R

Code Number: jp06085

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 CYP2D6FNx014 and CYP2D6FNx0110 and thus study groups CYP2D6FNx014/FNx014, CYP2D6FNx014/FNx0110 and CYP2D6FNx0110/FNx0110. Such groups may not be easily found in other populations in the east or the west.

References

Copyright 2006 - Journal of Postgraduate Medicine