Circulating Chemerin Levels, but not the RARRES2 Polymorphisms, Predict the Long-Term Outcome of Angiographically Confirmed Coronary Artery Disease

• Published in: International journal of molecular sciences Vol. 20; no. 5; p. 1174
• Main Authors: Er, Leay Kiaw, Hsu, Lung-An, Juang, Jyh-Ming Jimmy, Chiang, Fu-Tien, Teng, Ming-Sheng, Tzeng, I-Shiang, Wu, Semon, Lin, Jeng-Feng, Ko, Yu-Lin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07-03-2019; MDPI
• Subjects: Adult; Aged; Aged, 80 and over; all-cause mortality; Angina; Angina pectoris; Angiography; Atherosclerosis; C-reactive protein; C-Reactive Protein - metabolism; Cardiovascular disease; chemerin; Chemokines - blood; Chemokines - genetics; Coronary artery; Coronary artery disease; Coronary Artery Disease - blood; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - genetics; Coronary vessels; Creatinine; Diabetes mellitus; Endothelium; Epidermal growth factor receptors; Female; Gene Expression Regulation, Neoplastic; Genome-Wide Association Study; Genomes; Heart diseases; Hematocrit; Homeostasis; Humans; Hypertension; Inflammation; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Kaplan-Meier Estimate; Male; Medical prognosis; Metabolism; Middle Aged; Mortality; Myocardial infarction; Polymorphism, Single Nucleotide; Population; Promoter Regions, Genetic; RARRES2 gene; Regression analysis; Risk analysis; Risk factors; Smooth muscle; Survival analysis; Taiwan; Up-Regulation; Taiwan; coronary artery disease; chemerin; RARRES2 gene; all-cause mortality; genome-wide association study
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20051174

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
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
gene promoter region polymorphism rs3735167 (
= 2.35 × 10
). In the CAD population, borderline significance was noted between
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
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
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.