The Rest of the Iceberg

In a recent post we used an analysis of Craig Venter’s genome to illustrate how much has yet to be learned about the relationship between genetic variation and health-related traits.

A new paper by Venter and colleagues at his Rockville, Maryland-based institute provides a prime example. Writing in the September issue of Clinical Phamacology & Therapeutics, Venter et al. argue that knowing how genetic differences between ethnicities affect patients’ reactions to certain medications isn’t good enough. To make sure patients get the best healthcare, they say, doctors should be looking at how each person is likely to respond to a particular drug regimen based on his or her unique genetic makeup.

“Even the term ‘Caucasian’ can be deceptive,” the authors noted. “If a self-identified Caucasian originates from a founder population in which certain disease-specific alleles occur at higher frequencies (e.g. Quebec French Canadians or Ashkenazi Jews), his or her doctor may miss an important aspect of the patient’s medical history. One’s ethnicity/race is, at best, a probabilistic guess at one’s true genetic makeup.”

To further emphasize the differences between people within the same ethnic group, the authors compare the publicly available genome sequences of Venter himself and Nobel Prize winner James Watson, focusing on six genes involved in drug metabolism.

One of those genes revealed a substantial difference between the two men. CYP2D6 is involved in the metabolism of various drugs for high blood pressure, heart arrhythmia and depression. Venter’s genotype indicates that like most Europeans he is an “extensive metabolizer” of such drugs; but Watson’s genotype puts him in the “intermediate metabolizer” category, which is more common among Asians.

Using race as a guide, the authors noted, a physician would have no reason to expect Venter and Watson to react differently to drugs that are metabolized by CYP2D6.

Venter and his colleagues conclude by emphasizing the need for personalized health care based on genomic information, adding that the cost to do so is dropping rapidly.

“Given the complex nature of drug responses, it would ultimately better serve all to dissect the relevant factors of a drug response instead of categorically stereotyping a culture with a presumed genetic background.”

Images: Venter photo by Michael Janich; Watson photo courtesy of the National Library of Medicine






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