The study is the latest in a growing body of research focused on pharmacogenetics, or how genetic factors influence a person's reaction to a specific drug. An unrelated study recently set off controversy when it found the heart drug BiDil was effective in treating African Americans after having fared poorly when given to Caucasians, causing concern that pharmacogenetics could lead to racially tailored drug marketing.

There are small, but sometimes important, differences in the structure of the same gene among different people. That is, the genotypes are slightly different. The study, by researchers in Korea, found that people with type 2 diabetes who had certain genotypes were less likely to show improvement in blood glucose control (as measured by A1C levels), fasting glycemia and plasma adiponectin levels (a marker for insulin sensitivity) after treatment with rosiglitazone (marketed as Avandia), as compared to other people with type 2 diabetes. Subjects were treated with the medication for 12 weeks without changing any of their previous medications.

"This study has nothing to do with race," said Dr. Eun Seok Kang, one of the lead researchers on the study. "It shows us how important pharmacogenetics could be in the future in helping us quickly and efficiently determine the best treatment to give people. If something in our genetic make-up offers clues about how well we will respond to particular medications, this could be a tremendous asset to people with diabetes and other complex diseases. Obviously knowing ahead of time which drugs will work best means we can eliminate the entire trial-and-error process of drugs that don't work or work poorly for some people. Clearly we have a lot more to learn before we get to that stage, but this is an important first step."

diabetes

The new findings also have implications for disorders such as flesh-eating staph infections and drug-resistant bacterial infections that are difficult to treat. The researchers note that in these cases, it might be possible to develop an inhibitor of IKKa that boosts the inflammatory response to better fight these infections. However, such an inhibitor should have a short half-life, so that its potential devastating effect can be properly terminated.

The Karin lab, which has made several of the past discoveries involving IKKb ™s pro-inflammatory role, has also studied IKKa over the years, but they have identified roles unrelated to the primary inflammatory response. For example, in 2001, the investigators determined that IKKa was essential for formation of the skin ™s outer layer.* In a follow-up study, the team found clues that IKKa may be more involved in the immune response than they previously thought, but its role still appeared limited.** The current study is the first, however, to specifically show the novel mechanisms used by the protein to control the duration of an inflammatory response.

The study was funded by the National Institutes of Health. The co-first authors were Toby Lawrence, Ph.D., and Magali Bebien, Ph.D., post-doctoral fellows in the Laboratory of Gene Regulation and Signal Transduction, UCSD Department of Pharmacology. Currently, Lawrence is an assistant professor and member of the Faculty of Medicine, Imperial College London. Additional authors were George Liu, Ph.D., UCSD Division of Pediatric Infectious Diseases, UCSD School of Medicine; and Victor Nizet, M.D., associate professor of pediatrics, UCSD School of Medicine.

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