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Samuel J. Mann, M.D.

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Genetics and Personalized Drug Therapy of Hypertension: Don't Expect Too Much

Posted: 10/03/2012 10:58 am

The most exciting and hyped news this week in medical research regarding drug therapy was about the drug treatment of cancer. Recent studies showed that genetic characterization of cancer tissue can identify specific molecular targets, enabling selection of the drugs that best fit an individual's cancer, with much higher success rates.

Many hypertension studies are also tackling the exact same question: If we can identify the genetic variant or variants responsible for a patient's hypertension, could we then identify the drugs best suited for him or her? Although they have raised hopes that treatment of hypertension can soon be personalized in this way, I don't think that is likely to happen soon. Here are two reasons why:

The main problem is that research has thus far identified dozens of genetic variants linked to development of hypertension, with more to come. Each is responsible for a tiny piece of the puzzle, and in the usual case, hypertension cannot be attributed to any one or two genes. Most of us, whether we have hypertension or not, likely harbor any number of genetic variants that can contribute to hypertension. Even if you don't have hypertension, you could be carrying eight genetic variants associated with hypertension, while someone with hypertension is carrying six. Right now, a family history of hypertension provides much more helpful information about genetic predisposition than does a genome-wide scan.

Another major difference between hypertension and cancer is that the development of hypertension is much less governed by genetic factors than is cancer. With hypertension, lifestyle factors, such as weight, diet, salt intake, exercise, and psychological factors, play a much more important role, with genetics determining only about 30 to 60 percent of hypertension. In other words, if you have only a mild genetic predisposition but have poor health habits, you are more likely to develop hypertension than someone with somewhat greater genetic risk, but a healthy lifestyle.

That is why genetic research is less likely to tell us who needs which drug. Does that mean that physicians have no tools to help them pick out the right drug? No. As I explain in Hypertension and You, there are many overlooked clinical clues that can help guide physicians in selecting drugs. They include clues of excessive salt and volume retention, such as edema (fluid retention in the legs), biochemical clues, such as renin level, race and age, that point us to focus on a diuretic. Overlooked psychological clues can help identify who has hypertension that is mainly psychologically driven, and who are more likely to respond to a different set of medications.

So, unlike the treatment of cancer, the future of personalized drug selection in treating hypertension is not likely to result from filling in a genetic map. It lies instead in understanding better, and making better use of, the clinical clues that can guide us.

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