HealthDay News – Mutations in the angiopoietin-like 4 (ANGPTL4) gene are associated with coronary artery disease (CAD), according to 2 studies published online March 2 in the New England Journal of Medicine.
Frederick E. Dewey, MD, from the Regeneron Genetics Center in Tarrytown, New York, and colleagues sequenced the exons of ANGPTL4 in samples from 42 930 participants in the DiscovEHR human genetics study. Researchers identified 1661 heterozygotes and 17 homozygotes for the E40K variant and 75 other participants with monoallelic inactivating mutations in ANGPTL4. Carriers of the E40K variant had levels of triglycerides that were 13% lower and levels of high-density lipoprotein cholesterol that were 7% higher than noncarriers. Compared with noncarriers, E40K variant carriers were less likely to have CAD (odds ratio [OR]: 0.81).
Nathan O. Stitziel, MD, PhD, from the Washington University School of Medicine in St. Louis, and colleagues tested 54 003 coding-sequence variants covering 13 715 human genes in up to 72 868 patients with CAD and 120 770 controls. Researchers identified significant associations for CAD and low-frequency missense mutations in SVEP1 (OR:1.14) and ANGPTL4 (OR: 0.86). Nine carriers of loss-of-function mutations in ANGPTL4 were identified in 6924 patients with myocardial infarction, compared with 19 carriers among 6834 controls (OR: 0.47). Carriers of loss-of-function alleles in ANGPTL4 had 35% lower triglyceride levels.
“We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease,” Dr Stitziel and colleagues wrote.
Disclosures: The Dewey study was funded by Regeneron Pharmaceuticals.
- Dewey FE, Gusarova V, O’Dushlaine C, et al. Inactivating variants in ANGPTL4 and risk of coronary artery disease. N Engl J Med. 2016. doi: 10.1056/NEJMoa1510926.
- Kersten S. The genetics of dyslipidemia—when less is more. N Engl J Med. 2016. doi:10.1056/NEJMe1601117.
- Myocardial Infarction Genetics and CARDIOoGRAM Exome Consortia Investigators. Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease. N Engl J Med. 2016. doi: 10.1056/NEJMoa1507652.