Rare damaging mutations that are highly associated with increased triglyceride levels and presence of coronary artery disease (CAD) were identified by an SKKU and Harvard Medical School joint research team. Together with Drs. Amit KHERA and Sekar KATHIRESAN (Massachusetts General Hospital, Harvard Medical School and Broad Institute), Prof. Hong Hee WON in Samsung Advanced Institute for Health Sciences and Technology (SAIHST) at SKKU and Samsung Medical Center analyzed DNA sequences of the lipoprotein lipase (LPL) gene of 46,891 individuals. In this cross-sectional study of CAD casecontrol studies, gene sequencing identified a damaging mutation in the LPL gene in 188 of 46,891 individuals (0.4%).
These mutations were associated with an increase of 19.6mg/dL in plasma triglycerides. In particular, these mutations were associated with increased odds of early-onset CAD with an odds ratio of 1.84. This research team previously published that rare mutations in the APOC3 (NEJM 2014), APOA5 (Nature 2015), ANGPTL4 (NEJM 2016) genes associated with plasma triglycerides and risk for CAD. These genes are known to be involved in hydrolyzing triglycerides in lipoproteins in the LPL pathway. “We, as a team, pursue successful combinations of advanced informatics skills and biomedical technologies to understand the genetic bases of human disease and improve healthcare,” Prof. WON mentioned. “In order to prevent cardiovascular disease, it is very important to control plasma triglyceride levels as well as LDL cholesterol. I hope this finding leads to the development of drugs for targeting LPL and related proteins and controlling triglycerides so that it can help maintain people’s health by preventing cardiovascular disease.” This research was published in the Journal of American Medical Association (JAMA) in 2017, with the title of “Association of Rare and Common Variation in the Lipoprotein Lipase Gene with Coronary Artery Disease.”