Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2, and response to niacin therapy

Sony Tuteja, Lu Wang, Richard L. Dunbar, Jinbo Chen, Stephanie Derohannessian, Santica M. Marcovina, Marshall Elam, Ellis Lader, Daniel J. Rader

Research output: Contribution to journalArticle

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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: Coding variants, rs7314976 (p.R311C) and rs2454727 (p.M317I), were genotyped in 2067 participants from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial. AIM-HIGH was a randomized, placebo-controlled trial that was conducted to assess the effect of extended-release niacin in patients with cardiovascular disease aggressively treated with low-density lipoprotein cholesterol-lowering therapy. 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.

Original languageEnglish (US)
Pages (from-to)285-293
Number of pages9
JournalPharmacogenetics and Genomics
Volume27
Issue number8
DOIs
StatePublished - Jan 1 2017

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Niacin
Carboxylic Acids
Hydroxyl Radical
Lipoprotein(a)
Alleles
Therapeutics
LDL Cholesterol
Cardiovascular Diseases
Placebos
Lipids
HDL Cholesterol
Triglycerides
Randomized Controlled Trials
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Tuteja, S., Wang, L., Dunbar, R. L., Chen, J., Derohannessian, S., Marcovina, S. M., ... Rader, D. J. (2017). Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2, and response to niacin therapy. Pharmacogenetics and Genomics, 27(8), 285-293. https://doi.org/10.1097/FPC.0000000000000289

Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2, and response to niacin therapy. / Tuteja, Sony; Wang, Lu; Dunbar, Richard L.; Chen, Jinbo; Derohannessian, Stephanie; Marcovina, Santica M.; Elam, Marshall; Lader, Ellis; Rader, Daniel J.

In: Pharmacogenetics and Genomics, Vol. 27, No. 8, 01.01.2017, p. 285-293.

Research output: Contribution to journalArticle

Tuteja, S, Wang, L, Dunbar, RL, Chen, J, Derohannessian, S, Marcovina, SM, Elam, M, Lader, E & Rader, DJ 2017, 'Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2, and response to niacin therapy', Pharmacogenetics and Genomics, vol. 27, no. 8, pp. 285-293. https://doi.org/10.1097/FPC.0000000000000289
Tuteja, Sony ; Wang, Lu ; Dunbar, Richard L. ; Chen, Jinbo ; Derohannessian, Stephanie ; Marcovina, Santica M. ; Elam, Marshall ; Lader, Ellis ; Rader, Daniel J. / Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2, and response to niacin therapy. In: Pharmacogenetics and Genomics. 2017 ; Vol. 27, No. 8. pp. 285-293.
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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: Coding variants, rs7314976 (p.R311C) and rs2454727 (p.M317I), were genotyped in 2067 participants from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial. AIM-HIGH was a randomized, placebo-controlled trial that was conducted to assess the effect of extended-release niacin in patients with cardiovascular disease aggressively treated with low-density lipoprotein cholesterol-lowering therapy. 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.",
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AU - Wang, Lu

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AU - Chen, Jinbo

AU - Derohannessian, Stephanie

AU - Marcovina, Santica M.

AU - Elam, Marshall

AU - Lader, Ellis

AU - Rader, Daniel J.

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N2 - 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: Coding variants, rs7314976 (p.R311C) and rs2454727 (p.M317I), were genotyped in 2067 participants from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial. AIM-HIGH was a randomized, placebo-controlled trial that was conducted to assess the effect of extended-release niacin in patients with cardiovascular disease aggressively treated with low-density lipoprotein cholesterol-lowering therapy. 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.

AB - 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: Coding variants, rs7314976 (p.R311C) and rs2454727 (p.M317I), were genotyped in 2067 participants from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial. AIM-HIGH was a randomized, placebo-controlled trial that was conducted to assess the effect of extended-release niacin in patients with cardiovascular disease aggressively treated with low-density lipoprotein cholesterol-lowering therapy. 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.

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