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 B.; Lader, Ellis; Rader, Daniel J.

doi:10.1097/fpc.0000000000000289

Cited by 11 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The characteristics of included studies are shown in Table 1. Among 42 eligible studies, 14 studies intervened with prebiotics (24, 29-39, 46, 47), 10 with probiotics (40,41,43,(48)(49)(50)(51)(52)(53)(54), 6 with synbiotics (24,44,(55)(56)(57)(58), 10 with microbial metabolites (27,28,(59)(60)(61)(62)(63)(64)(65)(66), and the remaining 4 with fecal microbiota transplantation (FMT) (24,25,45,67). Among these studies, 24) not only explored the respective but also the synergetic efficiency of FMT and the prebiotics on MetS.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials

et al. 2021

View full text Add to dashboard Cite

Background and aims: Metabolic syndrome (MetS), accompanied with significant intestinal dysbiosis, causes a great public health burden to human society. Here, we carried out a meta-analysis to qualify randomized controlled trials (RCTs) and to systematically evaluate the effect of microbial therapy on MetS.Methods and results: Forty-two RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. Pooled estimates demonstrated that treatment with microbial therapy significantly reduced the waist circumference (WC) (SMD = −0.26, 95% CI −0.49, −0.03), fasting blood glucose (FBG) (SMD = −0.35, 95% CI −0.52, −0.18), total cholesterol (TC) (SMD = −0.36, 95% CI −0.55, −0.17), low-density lipoprotein cholesterol (LDL-C) (SMD = −0.42, 95% CI −0.61, −0.22), and triacylglycerol (TG)(SMD = −0.38, 95% CI −0.55, −0.20), but increased the high-density lipoprotein cholesterol (HDL-C) (SMD = 0.28, 95% CI.03, 0.52). Sensitivity analysis indicated that after eliminating one study utilizing Bifidobacteriumlactis, results became statistically significant in diastolic blood pressure (DBP) (SMD = −0.24, 95% CI −0.41, −0.07) and in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD = −0.28, 95% CI −0.54, −0.03), while the body mass index (BMI) showed significant difference after eliminating one study utilizing oat bran (SMD = −0.16, 95% CI −0.31, −0.01). There was still no significant effect in systolic blood pressure (SBP) and in hemoglobin A1c (HbA1c%).Conclusion: In patients with MetS, the conditioning with microbial therapy notably improves FBG, TC, TG, HDL-C, LDL-C, WC, BMI (except for the study using oat bran), HOMA-IR, and DBP (except for the Study using Bifidobacteriumlactis), however, with no effect in SBP and in HbA1c%.

show abstract

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Currently, clinical studies evaluate the efficacy of nicotinic acid in combination with statins in reducing relevant clinical endpoints, including progression of cardiovascular disease, the incidence of major cardiovascular events, and associated mortality. It was observed that SNPs in GPR109A determine response to therapy by niacin in the lowering of lipoproteins [ 164 ]. A recent epidemiological analysis of adverse reactions with niacin indicated severe GI symptoms and anxiety.…”

Section: Lipid Metabolitesmentioning

confidence: 99%

Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Strassheim

Sullivan

Irwin

et al. 2021

Cells

View full text Add to dashboard Cite

G protein-coupled receptors (GPCRs) have originally been described as a family of receptors activated by hormones, neurotransmitters, and other mediators. However, in recent years GPCRs have shown to bind endogenous metabolites, which serve functions other than as signaling mediators. These receptors respond to fatty acids, mono- and disaccharides, amino acids, or various intermediates and products of metabolism, including ketone bodies, lactate, succinate, or bile acids. Given that many of these metabolic processes are dysregulated under pathological conditions, including diabetes, dyslipidemia, and obesity, receptors of endogenous metabolites have also been recognized as potential drug targets to prevent and/or treat metabolic and cardiovascular diseases. This review describes G protein-coupled receptors activated by endogenous metabolites and summarizes their physiological, pathophysiological, and potential pharmacological roles.

show abstract

“…It also plays a role in T cell proliferation 32 and is an Alzheimer's disease risk gene 33 . HCAR2 (hydroxyl-carboxylic receptor 2) is a niacin receptor gene that mediates niacin decrease of Lipoprotein(a) 34 . Nicotinic acid action on HCAR2 causes atherosclerosis to regress in humans and mice.…”

Section: Lipid Metabolismmentioning

confidence: 99%

HDAC9 Polymorphism Alters Blood Gene Expression in Patients with Large Vessel Atherosclerotic Stroke

Shroff

Ander

Zhan

et al. 2018

Transl. Stroke Res.

View full text Add to dashboard Cite

The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there remains a need to better understand this HDAC9 polymorphism's contribution to large vessel stroke. In this pilot study, we evaluated whether the HDAC9 polymorphism rs2107595 is associated with differences in leukocyte gene expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155 patients (43 LVAS and 112 vascular risk factor controls). RNA isolated from blood was processed on whole genome microarrays. Gene expression was compared between HDAC9 risk allele-positive and risk allele-negative LVAS patients and controls. Functional analysis identified canonical pathways and molecular functions associated with rs2107595 in LVAS. In HDAC9 SNP rs2107595 risk allele-positive LVAS patients, there were 155 genes differentially expressed compared to risk allele-negative patients (fold change > |1.2|, p < 0.05). The 155 genes separated the risk allele-positive and risk allele-negative LVAS patients on a principal component analysis. Pathways associated with HDAC9 risk allele-positive status involved IL-6 signaling, cholesterol efflux, and platelet aggregation. These preliminary data suggest an association with the HDAC9 rs2107595 risk allele and peripheral immune, lipid, and clotting systems in LVAS. Further study is required to evaluate whether these differences are related to large vessel atherosclerosis and stroke risk.

show abstract

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

Cited by 11 publications

References 48 publications

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials

Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

HDAC9 Polymorphism Alters Blood Gene Expression in Patients with Large Vessel Atherosclerotic Stroke

Contact Info

Product

Resources

About