I was reading an article online from the New York Times (http://www.nytimes.com/2012/05/18/science/many-rare-mutations-may-underpin-diseases.html?_r=1&ref=health) and it brings up a problem with most genetic views of chronic illness. There was a sort of unspoken doctrine in those looking for genetic precursors of illness; that is, that if the illness is common, the genetic difference will be common. It was a good idea, a hopeful idea, but very naive. Unfortunately most genetic literature I read today still shares this idea.
As full genetic sequencing (still too expensive to use in routine medical practice) has become more and more available, it has become clear that there are many more changes in each of us than we had previously thought. Let me point out a good example of that.
I’ve written before about MTHFR, a gene that produces an enzyme responsible for the production of L-methylfolate, which is, in its turn, required for good dopamine synthesis. Almost everyone who studies MTHFR looks at a single SNP, rs18001133, and occasionally at another, rs18001131. If a physician orders the test from a regular lab, they only get the answer for those two SNPs and bases the decision on whether or not to prescribe L-methylfolate on the answer to those two SNPs alone.
However, I’ve had the chance to look at over 100 SNPs in MTHFR for quite a few people who have responded to L-methylfolate as part of a treatment for addiction. There are other polymorphisms that can increase a person’s likelihood to respond to L-methylfolate and some that seem to make it unnecessary. This calls into question the conclusions of almost all modern genetic research in common illnesses.
Taking addiction for example, so many people look at one SNP and then report that they have found a significant difference in the prevalence of that SNP in a population with addiction using a certain substance. It’s easy to get these papers published. The problem is that they will not impact effective treatment much at all.
First we will require a good definition of addiction, which ASAM has provided us with just recently. ( http://www.asam.org/for-the-public/definition-of-addiction ). Then we will require whole genome sequencing of large numbers of people. The work of 23andme and other GWAS providers is just a beginning. I know that the public has a great amount of hope for genetic testing in disease, and it has already proven valuable to some with addiction, but this is still in its infancy and much, much more is yet to come.
© Howard C Wetsman MD FASAM 2012