Abstract 18143: Impact of FMO3 Gene Loss-of-Function Variants on Coronary Artery Disease in Japanese

High-fat foods are rich in the lipid phosphatidylcholine, which is converted to trimethylamine by intestinal bacteria and then processed to harmful metabolite, trimethylamine N-oxide (TMAO), by key enzyme flavin containing monooxygenase 3 (FMO3) in the liver. TMAO has been liked to heart disease in human metabolomic studies, and accelerates foam cell formation and atherosclerosis in animal models. We hypothesize that loss-of-function variants of FMO3 can be atheroprotective in coronary artery disease (CAD) high-risk population. Methods: Coding regions of FMO3 gene were analyzed with high-resolution melting method followed by direct sequencing in total of 506 patients (255 males, mean age of 58 ± 13) suspected CAD in our lipid clinic including 191 patients with genetically confirmed heterozygous familial hypercholesterolemia (FH). Coronary stenosis index (CSI) was estimated with angiography in 203 patients (118 males, mean age of 59 ± 12) including 61 patients with FH. Fasting lipid profiles without lipid-...