Pharmacogenetics and genetic polymorphisms

In the theoretically correct application of the term, Pharmacogenetics is the study of inherited variations in drug response. Strictly, it would apply to germ line mutations (genetic polymorphisms) and not to somatic mutations or to epigenetic mechanisms (unless these can be inherited).

Genetic polymorphism occurs when the "simultaneous occurrence in the same locality of two or more alleles is in such proportions that the rarest of them cannot be maintained just by recurrent mutation". This conventionally assumes that the rarest allele should be more than 1%.

There are two parts to this definition.

a] it must refer a population in equilibrium; although I use this term guardedly, since no population is static and is truly ever in 'equilibrium'.

b] the frequency of the rarest allele is at least 1%. This is very empirical as it is not certain what is the barest minimum frequency for the allele to be propagatable in a given population. It would seem that 1% is too high a value, and genetic polymorphisms do refer to alleles with frequencies much less than 1%. It does not however, include mutations that occur sporadically and randomly. Consequently allele frequencies for a genetic polymorphism are often tested against the Hardy-Weinberg Equilibrium. If it does not fit the HWE, it does not necessarily mean it is not a genetic polymorphism. It just cautions the investigator to look reasons why the HWE has been violated.

One particular consideration that is often overlooked in determining allele frequencies in a genetic polymorphism (which may or may not cause deviations from the HWE), is whether the population is stable and if there is a real equilibrium with respect to the transmission of alleleic variants. This is a particular problem for Singapore, whose population has been growing at a phenomenal rate through immigrations, and the expansion of our foreign worker pool. Recent additions to the population now may begin to outnumber those that are born locally. This raises questions about whether the population genetic pool is too labile to be in any sort of equilibrium. It could only be if we are able to assume that the larger population base of people of similar "race/ethnicity" are in equilibrium globally. But this is not a valid assumption.