Sylvia Stankov, Cecilia Vitali, Joseph Park+9 more · 2023 · medRxiv : the preprint server for health sciences · Cold Spring Harbor Laboratory · added 2026-04-24
Plasma triglycerides (TGs) are causally associated with coronary artery disease and acute pancreatitis. Apolipoprotein A-V (apoA-V, gene We used hydrogen-deuterium exchange mass spectrometry to determ Show more
Plasma triglycerides (TGs) are causally associated with coronary artery disease and acute pancreatitis. Apolipoprotein A-V (apoA-V, gene We used hydrogen-deuterium exchange mass spectrometry to determine the secondary structure of human apoA-V in lipid-free and lipid-associated conditions and identified a C-terminal hydrophobic face. Then, we used genomic data in the Penn Medicine Biobank to identify a rare variant, Q252X, predicted to specifically eliminate this region. We interrogated the function of apoA-V Q252X using recombinant protein Human apoA-V Q252X carriers exhibited elevated plasma TG levels consistent with loss of function. Deletion of apoA-V's C-terminus leads to reduced apoA-V bioavailability Show less