Genes-R-Us —Carrier status and drug response

Genes-R-Us —Carrier status and drug response

Posted: Wednesday, November 9, 2011 5:02 pm

Your parents unwittingly dealt you a genetic “hand” that can be anywhere from protective to high risk. Last week we investigated how to interpret the risk of diseases that have both a genetic component (nature) and an environmental component (nurture). The genetic variants that influence the onset of these polygenic diseases — e.g., involving multiple genes like type-2 diabetes — are complicated by nurture. 
How we live has a big impact on whether we develop polygenic diseases. 
A fascinating case is the Dutch woman, Hendrikje van Andel-Schipper, who died in 2005 at 115. Ahead of her time, she donated her body to science 30 years before her death. She had genetic predispositions associated with a whole host of age-related diseases such as Alzheimer’s and heart disease, yet she developed none of these.
An autopsy on Ms. Andel-Schipper revealed zero signs of clogged arteries, no signs of the protein buildup in her brain that is the hallmark of Alzheimer’s disease and no signs of dementia, even up to her last day. She did not smoke and limited her alcohol consumption and ate lots of herring. 
Ahem … she also had no children and did not marry until age 49. Her husband died after 20 years of marriage; she did not remarry. She lived independently until age 105. Remarkable.
There is a simpler class of disease where genetics dominates. For the most part, these diseases are monogenic, i.e., caused by a problem with a single mutated gene, and are inherited in a recessive manner. They typically have uncommon names like hemochromatosis (he-mo-chro-ma-toe-sis). If you have one of these diseases, then chances are pretty high that you already know about it. But what you may not know is that you can pass some of these particular nasty diseases as a carrier without having the disease yourself. Let’s revisit that “recessive” concept.
Recessive means that an individual must inherit a “bad” (mutated) version of the gene from both parents to develop the disease. And it really can be just one unlucky “letter” that you received from both mom and dad out of your three billion-plus-lettered genome. My father found out he was a carrier of Cystic Fibrosis from direct-to-consumer (DTC) genetic testing. I did not inherit the mutated gene from him, thus I am not a carrier. With four biological daughters, chances are high that one of my father’s other three daughters is a carrier.
In DTC genetic testing, you can expect to learn your carrier status for around 30 of these monogenic baby-bombs. Like everything else in DTC genetic testing, carrier status gets updated as the science progresses. Tay-Sachs is a monogenic disease where improper storage of fatty acids causes a fatal deterioration of neurological and physical abilities. Tay-Sachs has a reputation for being a Jewish disease, but 1 out of 300 people are estimated to be a carrier and — surprise — it also runs in French Canadian, Louisiana cajuns and the Irish populations. 
Let’s switch gears from disease to the drugs that are used to treat disease. 
We know that the same medication can work very well for some people but not for others. Not everyone has the side-effect profile to a given drug. This is because medications interact with the proteins for which our genes carry the recipes. 
We can have different proteins, sometimes non-functional altogether, if we have different versions of genes in our genomes. DTC genetic testing companies measure that variation in our genomes using SNPs (pronounced snips-single “letter” changes in DNA between people).
Pharmacogenomics (phar-ma-co-ge-no-mics) is the name given to the science that studies the interaction between drugs and our genomes. DTC genetic testing provides several dozen pharmacogenomics results.  
For example, I have learned that I will need a lower than normal dose of the blood thinner Coumadin®. Plavix®, which is used to prevent blood clots, will not work very well on me. And beta blockers will work no better on me than a placebo. I hope to need none of these drugs, but my crystal ball is cloudy.
On a lighter note — I drink coffee with even greater delight, knowing now that I am a fast metabolizer of caffeine. Yes, caffeine is a drug that I enjoy daily. I am happy, and Starbucks is happy.
But if I wasn’t happy, I now know that I have typical odds of successful remission from depression should I take any of the following antidepressants: Elavil, Paxil, Effexor or Celexa.  
Genomics has taken “better living through chemistry” to a whole new level.
Editor’s note: Nancy Miller Latimer has worked in scientific research and development for 27 years. She blogs at neuronalbeauty.blogspot.com. Published in The Messenger 11.9.11

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