SNPwatch: Genetic Variants Affect Weight Loss Drug Effectiveness

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Obesity affects about one out of three adults in the United States. And because obese people are at increased risk of high blood pressure, diabetes, cardiovascular disease and other health problems, many authorities consider it one of the most significant public health problems in the developed world.

Of course diet and exercise are important parts of maintaining a healthy weight, but some people need a little more help. Sibutramine (marketed by Abbott Laboratories as Meridia ® in the U.S.) is a drug that creates a feeling of fullness, prevents the decline in metabolic rate usually associated with low calorie diets and causes weight loss, especially when combined with behavioral therapy.

But success with sibutramine is variable — for some people it just doesn’t work. New research, published in the October issue of Gastroenterology, shows that genetic differences might be to blame.

“Our results suggest the genetic make-up of patients could predispose their responsiveness to a drug. This could have important implications for the future of personalized molecular-based or individualized medicine,” said the study’s lead author Dr. Michael Camilleri in a statement.

(A video of Dr. Camilleri describing his research can be found at the end of this post.)

Using a sample of 158 overweight and obese people, researchers at the Mayo Clinic tested the effectiveness of sibutramine therapy compared to placebo over 12 weeks. All participants also received behavioral therapy.

The researchers found that weight and body mass index were significantly reduced in patients taking sibutramine compared to placebo, as was expected from previous research. But upon further inspection of the data, the researchers found that only people with certain versions of three different genes experienced significant weight loss.

People with at least one T at the SNP rs5443, in the GNβ3 gene, had success with sibutramine, losing about 13 pounds. People with at least one T at rs5443 and two Cs at rs1800544, in the α2A gene, lost even more weight — more than 17 pounds on average. The drug had no effect if a person had two Cs at rs5443.

The third genetic marker scientists investigated, known in the scientific literature as 5-HTTLPR, is a stretch of DNA that comes in a long and short form. Only people with one or two copies of the short version of this marker had significant weight loss with sibutramine. 23andMe does not currently give data for this type of variant.

“Genetic variations may help select obese patients who are more likely to experience improved outcome with this treatment. Since the different markers were present in almost 50 percent of patients, inclusion of screening for the genetic markers before prescribing the medication may even be cost-effective from a public health perspective,” Camilleri said.