October 24, 2006

Pharmacogenetics or the Science of Side effects

I was reading papers at the website of the Genomas company tonight, owner of LPH or the Laboratory of Personalized Health, which does genetic testing to determine whether individuals are susceptible to certain drugs' side effects.

The science behind this was discussed by Genomas founder and researcher Gualberto Ruano at the NAMI-CT Fourth Annual Conference Joe and I attended on the same Saturday that Lynnie and I were Keynote speakers there, and he was fascinating. Let me see if I can explain in brief what he talked about.

Many drugs, including psychiatric drugs, are metabolized in the liver by what are known as the CYP enzymes. These are proteins that help break down drugs, read by the body as toxic compounds, into detoxified and hopefully useful products. Adverse drug reactions -- ADRs -- often occur because poorly metabolized drugs remain in the body in their toxic forms. The idea behind genetic testing is to determine what kind of drug metabolism a person has: whether one is a ultrarapid metaboliser (needing a very high dose of medication because the drug is broken down so fast and disappears from the system in no time) a normal metabolizer (only 50%), for whom the recommended doze is adequate or a intermediate (40%) or null metabolizer (6%). The null metabolizer in particular cannot detoxify the drug and should not be given it at all. The intermediate metabolizer should be given low doses and carefully monitored for drug interactions and ADRs, which may be anticipated.

How does one tell a good or superfast metabolizer from a poor or null one? Here's where genetics comes in. By means of a blood sample alone, DNA typing allows a patient's metabolic proficiency to be characterized for each drug by using the CYP family of enzymes. The gene that codes for the enzyme is present in two copies in each of us, one copy from our mother and one from our father, and each gene may represent a fully functioning enzyme, a partially functioning one, or a non-functioning one. In each individual there are several different combinations that may result, depending on the contributions of genes from the parents. If, say, one's mother has two functional genes and one's father one null and one deficient, and passes on the deficient gene, the child has one deficient gene and one functioning one...and therefore expresses an enzyme that is somewhat less than fully functional (due to the one copy that is deficient). If a person inherits two null copies, ie two completely dysfunctional genes, one from each parent, he or she cannot express the enzyme or metabolize the drug at all, and it remains toxic for as long as it remains in the body. The ultrarapid metabolizer, 1% of the population, apparently has duplicate copies of the gene, which apparently codes for super-efficient detoxification.

This sort of DNA-typing information is so valuable that the FDA has incorporated it into its prescribing policies where possible, warning that poor metabolizers of certain drugs have elevated plasma levels of a drug compared to the norm and that lab tests are available to identify such poor metabolizers. One day this may be the case for all our medications, and it may no longer be a case of trial and error at least to know which drugs we can or cannot tolerate.

For those who are interested in reading further, you can find more information at

Posted by pamwagg at October 24, 2006 07:38 PM


You explained it more clearly than I could and everyone appreciates that.

Posted by: Joe at November 6, 2006 06:22 PM

Hi Pam,
I saw Dr. Ruano at the NAMI-CT conference on Oct 14. I did not remember his name or all of the organizations he mentioned when I wrote you last time. The only one I remembered was the Institute of Living (IOL), which I am pretty sure is related to Genomas and the Laboratory of Personalized Health. He also said everything he is doing is associated with Hartford Hospital. His presentation was fascinating. Thank you for giving your summary. I bet Joe would be impressed by it. I know he is and "electrical" guy, but I think he is interested in anything scientific. I was definitely impressed with your summary.
Concerning your previous entry, I don't think L was saying you looked like you gained any weight. I think your own words could be paraphrased as,

"Then L said for him to stop bothering me, and said I did not look any different from when she say me the last time."

I think that is what L meant. Her main intent was to tell C to stop bothering you.

I think it was a good step and a courageous step for you to get on the scales. Now you have that information as a reference. I hope you can use that information in a wise manner (thank you very much for sharing that info with us). At that NAMI conference on Oct 14, I was so glad I could share lunch with you and with Joe (you did eat a full plate then which was great - the food there was great too). Like I said then, I hope you keep getting enough energy to keep doing what you are doing. We all want to keep hearing from you. Please take care,

Posted by: Stuart at October 25, 2006 11:15 AM

This science will be so helpful to anyone who takes medication. Thank you for posting the information.


Posted by: yaya at October 25, 2006 12:34 AM

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