null RI-MUHC team identifies new gene associated with risk of cardiovascular diseases

Authors Mary Hoekstra, M.Sc., George Thanassoulis, MD, and Jamie Engert, PhD.
Authors Mary Hoekstra, M.Sc., George Thanassoulis, MD, and Jamie Engert, PhD.

New study analyses millions of genetic variants in almost 300,000 individuals

Source: RI-MUHC. Despite tremendous scientific advances over the past decades, the worldwide death toll from cardiovascular diseases exceeds cancer, respiratory disease and diabetes combined.

Cholesterol is an important factor in cardiovascular disease. One type of cholesterol particle, known as Lp(a), can substantially increase the risk of cardiovascular diseases. Even in a patient with low levels of LDL, or “bad” cholesterol, the presence of this Lp(a) particle can increase disease risk, including heart attack and aortic stenosis.

In a new publication in the journal Atherosclerosis, Thrombosis and Vascular Biology, a team at the Research Institute of the McGill University Health Centre (RI-MUHC) has identified a gene that is associated with levels of Lp(a) in blood plasma.

Led by Jamie Engert, PhD, and George Thanassoulis, MD, from the Cardiovascular Health Across the Lifespan Program at the RI-MUHC, this new study used advanced biostatistical methods to analyse data from the United Kingdom Biobank.

In a project supervised by both RI-MUHC researchers, Mary Hoekstra, M.Sc., analysed millions of genetic variants in almost 300,000 individuals and identified a variant in the Apolipoprotein H (APOH) gene that affects Lp(a) levels in plasma. Previously, most genetic variations affecting Lp(a) plasma levels were from the LPA gene itself.

“Mary Hoekstra validated these findings in two American studies, the Framingham Offspring study and the Multi-Ethnic Study of Atherosclerosis,” says Dr. Thanassoulis. “These large, ongoing cardiovascular cohort studies are an important resource for research in cardiovascular disease.”

Adds Jamie Engert, “The APOH gene codes for the beta2-glycoprotein I protein, which can also be measured in plasma. But we don’t yet understand how this new genetic variant influences Lp(a) levels.”

Ultimately, APOH could become a target for the development of new drugs. “Future work in this area can have a big impact,” Mary Hoekstra says. “Even a small reduction in the risk of developing cardiovascular diseases could mean better health outcomes for millions of people.”

About the study:

Mary Hoekstra, Hao Yu Chen, Jian Rong, Line Dufresne, Jie Yao, Xiuqing Guo, Michael Y. Tsai, Sotirios Tsimikas, Wendy S. Post, Ramachandran S. Vasan, Jerome I. Rotter, Martin G. Larson, George Thanassoulis, James C. Engert. Genome-Wide Association Study Highlights APOH as a Novel Locus for Lipoprotein(a) Levels. Arterioscler Thromb Vasc Biol. 2020; 40:00–00. DOI: 10.1161/ATVBAHA.120.314965

November 18, 2020