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

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.

Evaluation of adipokine chemerin in hypertensive obese

“…This increase, with the positive correlation between hs-CRP and chemerin in hypertensive group may point to the fact that some sort of inflammation may influence the role of chemerin with hypertension. Some studies confirmed the association of circulating chemerin with hs-CRP and hypertension (ZYLLA et al, 2017;ER et al, 2019). In agreement with the present study, the researchers found that hs-CRP increased in hypertensive patients and its high levels were considered a predictor of hypertension development in prehypertensives and normotensives (SESSO et al, 2003;BAUTISTA et al, 2005).…”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…Moreover, a 4-week infusion of chemerin-9, an agonist of CMKLR1, induces a decrease in aortic atherosclerotic lesions in apolipoprotein E-deficient (ApoE -/-) mice [ 86 ], while in another study using the same animal model, the contrary effect was reported, showing that chemerin protein levels correlated with inflammatory markers and plaque formation [ 138 ]. In the same line, although the majority of studies suggest that chemerin circulating levels are associated with the presence and severity of atherosclerosis [ 127 , 129 , 130 , 132 , 139 , 140 , 141 , 142 ], there are also contradictory results [ 124 , 143 ].…”

Circulating chemerin level is associated with metabolic, biochemical and haematological parameters—A population‐based study

“…We analysed the association of chemerin level with multiple phenotypes, circulating inflammatory markers and adipokines in two studies that enrolled a relatively small number of participants with pre-existing CAD in Taiwan. 11,25 In order to fully understand the role of chemerin in human health and exclude the bias arising from the effect of medications in different ethnicities, studies with a large number of healthy participants are needed.…”