Abstract 18721: Diacylglycerol Kinase ? (DGKB) Genotype Predicts Response to Niacin Induced Flushing and Changes in Insulin in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) Trial

• Published in: Circulation (New York, N.Y.) N.Y.), 2013-11, Vol.128 (suppl_22)
• Main Authors: Tuteja, Sony, Qu, Liming, Dunbar, Richard L, Li, Mingyao, Mucksavage, Megan, DerOhannessian, Stephanie, Reilly, Muredach P, Rader, Daniel J
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.128.suppl_22.A18721

Abstract only Niacin has been used for decades as a lipid lowering agent but its use is limited by flushing. Stimulation of a G-protein coupled receptor (GPR109A) on immune cells of the skin by niacin results in generation of prostaglandinD 2 /E 2 and flushing. An evoked phenotype genetic study (termed the GENE study) was undertaken to determine genes associated with flushing and the findings were validated in the AIM-HIGH cohort receiving niacin. The GENE study recruited n=294 healthy volunteers (51% Female, 65% Caucasian (Cau)) to an IR 1 gm niacin challenge. Flushing was assessed by laser Doppler and quantified as the flux index (peak blood flow divided by baseline). In the AIM-HIGH cohort, 2100 Cau and 75 African-Americans (AA) subjects for whom DNA was available were classified as cases and controls based on flushing severity and frequency during the run-in period of the trial. Genotyping was performed on Human Cardio-Metabo BeadChip (Illumina). Insulin was assayed before and after niacin treatment was begun. In the GENE study, two independent loci in DGKB , a downstream mediator of GPCR signaling (lead SNPs Chr7:14349921, p=1 x 10 -6 and chr7:14281125, p=1.8 x10 -5 ) were associated with the flux index. Fasting insulin levels increased after niacin 94 ± 106% (p