Gene Variant For Protein In "Good" Cholesterol Keeps Jeans Loose

The protein, called apolipoprotein A-II (apo A-II) is a major component of high-density lipoprotein (HDL), sometimes referred to as “good cholesterol” due to its role in reverse cholesterol transport, the process by which cholesterol molecules are transported from the blood vessels and other tissues to the liver. If this process is defective, cholesterol molecules can accumulate in the arteries, helping to clog them and raising the risk of heart attack and stroke. There is evidence that increased levels of apo A-II can lead to slower removal of cholesterol and, ultimately, more build-up in the arteries.

“Animal studies have shown that apo A-II not only plays a role in reverse cholesterol transport, but is also important in other processes related to fat metabolism. However, until now, little has been known about its significance in human metabolism,” says lead researcher Ferdinand van ’t Hooft, M.D., Ph.D., of the Karolinska Institute, in Stockholm, Sweden. “This study provides the first evidence in humans for an extended role of apo A-II, in particular in relation to triglyceride and body fat accumulation.”

The researchers studied the effect of specific variations of the apo A-II gene in a group of 624 healthy, 50-year-old men. In these subjects, apo A-II concentration, levels of blood fats and quantity of body fat were related to a newly discovered, common genetic variation in the apo A-II gene called the 265T/C polymorphism.

They found that men with the 265C variant had lower apo A-II levels, decreased waist circumference and an enhanced metabolism of plasma triglycerides, compared to men with the 265T variant. Using cell culture systems, the researchers also demonstrated that the effect of the 265T/C polymorphism is probably related to its impact on the rate of production of apo A-II.

“This report underlines the multifunctional role of apo A-II, and indicates – among other things – that apo A-II influences waist size,” says van ’t Hooft. “More importantly, our study suggests that apo A-II can influence several different risk factors for coronary heart disease, indicating that this protein plays a critical role in the development of atherosclerotic disease.”

The discovery of the 265T/C polymorphism provides a novel genetic tool to test this hypothesis and to evaluate the proposed atherogenic properties of apo A-II in humans, he adds.

Co-authors are Giacomo Ruotolo, M.D., Ph.D.; Susanna Boquist, M.D., Ph.D.; Ulf de Faire, M.D., Ph.D.; Gösta Eggertsen, M.D., Ph.D.; and Anders Hamsten, M.D., Ph.D.