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.
Keywords: RARRES2 gene; all-cause mortality; chemerin; coronary artery disease; genome-wide association study.