Plasma Lipid Genetic Variants Associated With Response to Niacin
Participants in the placebo group who were homozygous for the minor allele had the highest rate of CAD-related death vs heterozygous carriers and homozygous major allele carriers.
Genetic variation at loci previously associated with steady-state lipid levels may be associated with response to niacin treatment, according to results published in the Journal of the American Heart Association.
In the past, genome-wide association studies have found a connection between multiple loci and blood lipid levels and lipoprotein. It is still not known whether these loci modulate in response to niacin. Given this, Sony Tuteja, PharmD, and colleagues “investigated whether genetic loci associated with basal lipid traits and [lipoprotein a] are associated with the change in plasma lipids and [lipoprotein a] on treatment with [extended release] niacin in the AIM-HIGH study [ClinicalTrials.gov Identifier: NCT00120289]”.
The AIM-HIGH study included 2054 participants who underwent genotyping and were randomly assigned to receive a statin drug plus placebo or a statin drug plus niacin in a variant-treatment interaction model. The investigators sought to determine whether genetic variations at validated loci were connected to a change in plasma lipid and lipoprotein level.
Investigators determined that there was a nominal significant interaction for genetic variants in MVK, LIPC, PABPC4, AMPD3 with change in high-density lipoprotein cholesterol, as well as with changes in low-density lipoprotein cholesterol in SPTLC3, total cholesterol changes for TOM1, and a change in triglycerides for PDXDC1 and CYP26A1.
Minor allele carriers at the LIPC locus in the placebo group saw an increased risk for coronary disease-related death (CI, 1.11-3.90, P =.02). Increased coronary disease-related death was not seen in the niacin group (P =.071). The placebo group also saw a greater risk for acute coronary syndrome (P =.02) and revascularization events (P =.002), but these increased risks were not seen in the group receiving niacin treatment in the major allele carriers at the CP26A1.
Researchers suggest that “genetic variation at loci previously associated with steady-state lipid levels display evidence for lipid response to niacin treatment.”
They also suggest that after independent studies and replications of this study have been concluded, clinicians will be able to use this information to identify patients who may benefit from niacin therapy.
Tuteja S, Qu L, Vujkovic M, et al. Genetic variants associated with plasma lipids are associated with the lipid response to niacin. J Am Heart Assoc. 2018;7(19):e03488.