Circulating chemerin levels, but not the RARRES2 polymorphisms, predict the long-term outcome of angiographically confirmed coronary artery disease
Journal
International Journal of Molecular Sciences
Journal Volume
20
Journal Issue
5
Date Issued
2019
Author(s)
Abstract
Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of RARRES2 polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the RARRES2 gene promoter region polymorphism rs3735167 (p = 2.35 × 10-21). In the CAD population, borderline significance was noted between RARRES2 polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan?Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with RARRES2 polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead RARRES2 polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
biological marker; C reactive protein; chemerin; creatinine; C reactive protein; chemerin protein, human; chemokine; signal peptide; adult; Article; blood cell count; body mass; clinical outcome; cohort analysis; coronary angiography; coronary artery disease; diabetes mellitus; DNA extraction; DNA polymorphism; enzyme linked immunosorbent assay; female; follow up; gene frequency; gene locus; genetic analysis; genetic association; genetic polymorphism; genome-wide association study; genotype; hematocrit; human; hypertension; immunoturbidimetry; inflammation; leukocyte count; major clinical study; male; middle aged; pathophysiology; platelet count; prognosis; quality control; risk factor; single nucleotide polymorphism; smoking; stable angina pectoris; survival rate; aged; angiography; blood; coronary artery disease; diagnostic imaging; gene expression regulation; genetics; Kaplan Meier method; metabolism; promoter region; single nucleotide polymorphism; Taiwan; upregulation; very elderly; Adult; Aged; Aged, 80 and over; Angiography; C-Reactive Protein; Chemokines; Coronary Artery Disease; Female; Gene Expression Regulation, Neoplastic; Genome-Wide Association Study; Humans; Intercellular Signaling Peptides and Proteins; Kaplan-Meier Estimate; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Taiwan; Up-Regulation
Publisher
MDPI AG
Type
journal article