Abstract | OBJECTIVE:
Niacin has been used for seven decades to modulate plasma lipids, but its mechanism of action is still unclear. We sought to determine whether variants in the niacin receptor gene, hydroxyl-carboxylic receptor 2 (HCAR2), are associated with lipid response to treatment. PARTICIPANTS AND METHODS: RESULTS: There was no association of p.R311C or p.M317I with changes in low-density lipoprotein cholesterol, triglycerides, or high-density lipoprotein cholesterol at 1 year in groups receiving placebo or extended-release niacin. In White patients, the reduction in lipoprotein (a) [Lp(a)] in response to niacin was greater in homozygous carriers of the major 317M allele (-22.7%; P=0.005) compared with minor allele carriers (-15.3%). This was directionally consistent in the Black participants. Upon combining both groups, the reduction in Lp(a) in response to niacin was significantly greater in the homozygous major allele carriers (-23.0%; P=0.003) compared with minor allele carriers (-15.2%). CONCLUSION: Understanding the genetic contribution toward variation in response to niacin therapy, including Lp(a) reduction, could uncover mechanisms by which niacin decreases Lp(a), an important independent risk factor for cardiovascular disease.
|
Authors | Sony Tuteja, Lu Wang, Richard L Dunbar, Jinbo Chen, Stephanie DerOhannessian, Santica M Marcovina, Marshall Elam, Ellis Lader, Daniel J Rader |
Journal | Pharmacogenetics and genomics
(Pharmacogenet Genomics)
Vol. 27
Issue 8
Pg. 285-293
(08 2017)
ISSN: 1744-6880 [Electronic] United States |
PMID | 28628560
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cholesterol, HDL
- Cholesterol, LDL
- Delayed-Action Preparations
- HCAR2 protein, human
- Hypolipidemic Agents
- Lipoprotein(a)
- Receptors, G-Protein-Coupled
- Receptors, Nicotinic
- Triglycerides
- Niacin
|
Topics |
- Adult
- Aged
- Cardiovascular Diseases
(drug therapy, ethnology, metabolism)
- Case-Control Studies
- Cholesterol, HDL
(blood)
- Cholesterol, LDL
(blood)
- Delayed-Action Preparations
- Female
- Genotyping Techniques
- Humans
- Hypolipidemic Agents
(administration & dosage, pharmacology)
- Lipoprotein(a)
(blood)
- Male
- Middle Aged
- Niacin
(administration & dosage, pharmacology)
- Polymorphism, Single Nucleotide
- Receptors, G-Protein-Coupled
(genetics)
- Receptors, Nicotinic
(genetics)
- Sequence Analysis, DNA
- Treatment Outcome
- Triglycerides
(blood)
- Young Adult
|