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By Keith Mulvihill
NEW YORK, Mar 29 (Reuters Health) - Researchers have uncovered more clues as to why some people have an easier time processing and removing drugs from their bodies compared to others.
It turns out that variation in a person's genes can call for the production of more or less of a group of enzymes that are essential in the breakdown and removal process of drugs, according to the report published in the April issue of Nature Genetics.
One of the keys to drug detoxification in the body is a family of enzymes known as CYP3A. This group of enzymes helps the body to rid itself of naturally occurring steroids, but they also help in the removal of certain medications. Members of the CYP3A family are known to inactivate half of all drugs, including HIV protease inhibitors, immune suppressing agents and anti-cancer chemicals.
While medications have beneficial effects when treating illness, they can be toxic and need to be broken down and removed, explained lead researcher Dr. Erin Schuetz of St. Jude Children's Research Hospital in Memphis, Tennessee.
Schuetz and colleagues examined tissue samples from organ donors and measured the amounts of specific enzymes in the CYP3A family and determined how active the enzymes were. The scientists discovered that one particular enzyme, CYP3A5, is produced with much greater variation than previously recognized.
"Originally, researchers thought that CYP3A5 was produced in about one quarter of the population. We now know that it appears in 30% to 80% of the population and largely is a function of a persons' genetic make-up," Schuetz told Reuters Health.
"Our study found that African Americans tend to make CYP3A5 more frequently compared to whites or Asians," Schuetz noted.
"While having more enzymes to remove toxins can be a good thing, some drugs when broken down, can create more toxic compounds," she explained.
"The bottom line is that drugs need to be studied on a case by case basis," Schuetz said. "This new information will one day allow genetic tests to determine who makes the CYP3A5 protein," which will allow researchers to tailor the drug dose to an individual's CYP3A5 genetic make-up so that the drug can work more efficiently.
The next step is to identify a person's genetic make-up for the production of CYP3A enzymes and monitor blood levels of drugs so researchers can gain a better understanding of the body's drug-breakdown relationship with a person's genes, Schuetz concluded.
SOURCE: Nature Genetics 2001;27:383-391.
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