Women with narcolepsy, a disorder characterized by excessive and overwhelming daytime sleepiness, respond differently than men to treatment with the drug modafinil. This difference may be due to a sex-specific variation in one gene. (The Pharmacogenomics J., Sep-2002)
Society for Women's Health Research (SWHR)
Women with narcolepsy, a disorder characterized by excessive and overwhelming daytime sleepiness, respond differently than men to treatment with the drug modafinil. This difference may be due to a sex-specific variation in one gene, according to results of a recent study. This finding adds to a growing body of evidence suggesting that so-called genetic polymorphisms -- tiny snippets of DNA that differ from one person to another -- may vary not only by race and ethnicity, but by sex too.
Since minute genetic differences can lead to big variations in an individual's response to medication, this and related studies suggest the days of sex-tailored medicines -- that is to say pink and blue pills -- may not be too far off. Pharmacogenomics is the burgeoning field of medicine examining the interactions between genes and drugs. Information gathered from this discipline promises to shape treatment plans to a patient's genetic profile, defined by the more than 30,000 genes contained in the cells of their body. The hope is that genetic screening can spot people most likely to respond to a particular medication while at the same time flag those at high risk of adverse drug reactions, which kill more than 100,000 Americans every year.
"The field of pharmacogenomics has blossomed in part because of an increased awareness that not everyone benefits or suffers side effects to the same extent from one drug," says Sherry Marts, PhD, scientific director of the Society for Women's Health Research. "This study suggests that a person's sex influences their probability of having a specific form of a gene, which can affect their response to certain medications."
Narcolepsy is a disabling disorder affecting approximately 100,000 people in the United States. Last year, Mehdi Tafti, PhD and colleagues at the Universite de Geneve in Switzerland found evidence implicating a gene called COMT in the severity of narcolepsy symptoms. COMT codes for an enzyme involved in processing a brain chemical called dopamine. The drug modafinil is thought to acting upon dopamine to alleviate narcoleptics' irresistible urge to sleep.
The researchers also reported that men and women tend to have different variations of COMT. The COMT gene has two forms: "L" which stands for low enzyme activity and "H" which represents high activity. Women in their study were more apt to have two copies of the L form of the gene whereas men tend to have the H form. In addition, the researchers found evidence to suggest that the drug modafinil works more efficiently at relieving symptoms of narcolepsy when the COMT enzyme is less active.
In their most recent work, the same group of researchers analyzed how 84 patients with narcolepsy responded to modafinil and how this related to the particular type of COMT gene they inherited. Once again, the researchers found that women were more likely to have the L form of the gene compared with men. In addition, the optimal dose of modafinil was an average of 100 mg lower among women compared with men. What's more, all patients with the L form of COMT needed a lower dose of modafinil to effectively control symptoms, confirming previous findings.
"The differences in daily dose between gender and COMT genotypes may
help individualization of modafinil treatment and highlight the importance
of understanding the genetic basis of variability in drug response," write
the researchers in their report published in The Pharmacogenomics Journal.
© 1995-2002 Newswise