“The things we hate about ourselves aren't more real than things we like about ourselves.” Ellen Goodman


Showing posts with label populations. Show all posts
Showing posts with label populations. Show all posts

Tuesday, November 16, 2010

Phytochemicals, pharmacogenetics and pharmacokinetics

When one appreciates the extensive range on interactions that exist between phytochemicals essentially entering our bodies through our diet, and the various processes involved in host protection, it becomes very clear that dietary modifications of pharmacokinetic process should be a relative given in our understanding of drug ADME. In fact it should be a central theme in our understanding of interindividual and interpopulational variability in drug behaviour, rather than just being accorded the occasional consideration as a determinant of drug behaviour.

As a corollary, pharmacogenetics cannot hope to fully explain the pharmacokinetic behaviour of any drug in an individual. Environmental chemicals, largely phytochemicals, modify pharmacokinetic processes according to the genetic constitution of the individual, while the genetic makeup of the individual can only be fully expressed in response to environmental chemical effects.

Which leads us to automatically consider what the epigenetic mechanisms might be, in shaping the PK environment of the individual. Perhaps these might be more important than the occasional loss/gain of function variants that we find in the population.

Friday, November 12, 2010

The Han Chinese - fiction or biological reality?

The Chinese people have been called various names. Once we were called Orientals; the word 'orient' referring to the East. The original reference to Orientals by the west was with respect to people from the middle east or asia minor- regions East of Europe. In time, the definition shifted eastwards and became more associated with East Asia. Clearly the term has no meaning today and should be completely dropped from the scientific literature. Another term, 'Asians' was sometimes used, although in the United Kingdom, this has come to refer to people from the Indian subcontinent. The term East Asians attempts to shift the definition towards people from China, Korea and Japan. For the most part, Chinese were just referred to as Chinese.

More recently however, another term 'Han Chinese' has emerged. The implication appears to be that the concept of Chinese was inadequate and that somehow a 'Han' preface was needed to distinguish Han Chinese from non-Han Chinese. I suspect this has arisen as a result of more scientific work from China, where it was necessary to distinguish the main Han ethnic group from the other 56 ethnic groups which were not 'Han'. The following chart shows the increasing use of the term 'Han Chinese' in the literature beginning from about 1980 and rising steeply over the last 10 years.
In Singapore we don't really care to be Han Chinese, other than using the term to be consistent with 1 billion other people who want to use the term. For us, we are just plain and simple Chinese.

The term Han Chinese actually takes reference to a wish to be associated with the legendary 1000 year Han dynasty which ended in 220CE. I think this is more important to the mainland Chinese, more of the northern sorts. Interestingly for many of us more southern type Chinese, of the Min-nan dialects, the term 'Tang people' '唐人' is more frequently used. This is in reference to another wonderful period of Chinese history called the Tang dynasty (618-904).

So there isn't a whole lot of consistency with respect to how Chinese people want to refer to themselves. Tracing an ancestry back to a dynastic period is not an ethnically reasonable proposition since there can be no assumption that people from that dynasty were necessarily ethnically homogeneous.

It is somewhat of a wishful thinking that the Chinese people, whether Han or Tang, are a biologically homogeneous bunch of people. For large stretches of Chinese history, the country had to deal with more belligerent northern neighbours, and had been conquered by Mongols and Manchus from the North. These people, clearly of a different ethnicity from the indigenous Chinese, not only tended to displace the populations southwards and also widely assimilated with the resident Chinese. The more southern Chinese didn't have the benefits of the Great Wall so there was really nothing to keep them from mingling with their more southern non-Han neighbours.

As a result of these admixtures, there is a north-south cline in East Asian populations. In China itself, there would appear at the very least, among the "Han Chinese", to be a distinction between northern and southern Chinese. The watershed for these two groups is not a clear one, but appear to be somewhere in the vicinity of the Yangtze or Chang Jiang river divide.

It is important to be aware of the existence of this cline because it affects the way we look at "East Asian" population data. While for the most part, Chinese data tend to cluster quite closely together (which is not surprising), we need to be careful about too readily extrapolating northern data to a southern Chinese population, and vice versa. In many situations, northern Chinese data seem to be more in alignment with data from Japan and Korea, while southern Chinese data aligns with Hong Kong, Taiwan and Singapore.

Singapore, being the most southern of the major 'Han Chinese' populations, may have some unique features potentially because of some degree of genetic admixtures with the resident austronesian populations in south east Asia.

Saturday, September 11, 2010

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.