Gene May Reveal Why Some Obese People Get High Blood Pressure

A gene that helps regulate appetite may explain why some people who are obese develop high blood pressure and others don’t.

A U.K. study tying the gene, MC4R, to high blood pressure may help doctors determine which obese patients are at greater risk of the condition, said Suzanne Steinbaum, a cardiologist at Lenox Hill Hospital in New York, who wasn’t involved in the research.

The study, published online today in the New England Journal of Medicine, is the first to link MC4R to weight gain and an increase in blood pressure, said author Sadaf Farooqi. Researchers said the finding may someday help doctors target high-blood pressure treatments for obese people. More studies are needed to understand better how MC4R affects the cardiovascular system.

“We know that worldwide at least 60 percent of all hypertension can be explained by obesity,” said Farooqi, a senior clinical fellow at the University of Cambridge in the U.K., in a Dec. 16 e-mail. “However, although many factors have been considered, we don’t fully understand why gaining weight is associated with an increase in blood pressure. This study provides evidence for the first time that the signal linking the two relates to MC4R.”

Scientists need to identify which genes determine the associations between obesity and other conditions such as diabetes, Farooqi said.

About two-thirds of U.S. adults are overweight or obese, and obesity is the No. 2 cause of preventable premature death in the U.S., behind smoking. Obesity raises the risk of heart disease, diabetes, cancer, high blood pressure, stroke and osteoarthritis, according to the U.S. Centers for Disease Control and Prevention, based in Atlanta.

Finding the Defect

Researchers measured the blood pressure of 46 adults who had a MC4R defect, which is linked to childhood obesity. The scientists then looked at an additional 30 adults who were either obese or overweight and had normal MC4R.

The researchers found that blood pressure was lower in those who had the defect. Researchers suggested a possible explanation: the interplay between leptin, a hormone that plays a role in metabolism, and MC4R.

Farooqi said weight gain increases levels of leptin, which works through the brain to activate MC4R, leading to a rise in blood pressure. In obese patients with a defective MC4R gene, the leptin increase doesn’t trigger a rise in blood pressure, she said.

The researchers took 26 of the overweight or obese adults who had a normal MC4R and gave them an infusion of Eli Lilly & Co.’s LY2112688, which stimulates MC4R. Those given the drug experienced an increase in blood pressure.

Focus on Complications

“A lot of research is being undertaken to understand why people gain weight and also to understand that when they gain weight why some people develop complications such as high blood pressure, whereas others don’t,” Farooqi said. “Not all obesity is the same.”

Development of LY2112688 was terminated in December 2005 while in the first of three phases of clinical trials, Christine Van Marter, a spokeswoman for Indianapolis-based Lilly, said in an e-mail yesterday.

Steinbaum said the study findings will have no bearing on current clinical practice.

“We have this pre-understanding that with increased weight we’re going to have increased blood pressure and that’s not always the case,” she said. This study answers “a question as to why this is happening. I wouldn’t want to change the practice of saying that if you gain weight your blood pressure is going to go up.”

Obesity is defined by body mass index, or BMI, a measurement that takes the patient’s weight in kilograms and divides by the square of the height in meters. A person with a BMI of at least 30 is considered obese; 25 to 29.9 is overweight and 18.6 to 24.9 is deemed normal.